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Biomedical subjects

T Cunningham

Publications and source records attributed to T Cunningham.

At least 19 recordsLinked to original sources
PubMed2000

Using online and offline change models to improve ICU access and revenues.

BACKGROUND: Hospital operational problems that span departments often present formidable challenges because they involve both processes and organizational relationships. Many improvement efforts fail because of relationship issues rather than a lack of understanding of system processes. Reflection on a recent change initiative led to the development of an integrated change model that includes both online and offline components. The online component draws on performance improvement models that provide concepts and tools for use in team meetings to improve processes. The offline component borrows from an earlier tradition of change management that offers guidelines for individuals or teams desiring to be change agents. METHODS: The integrated change model was applied in 1997 at The Johns Hopkins Hospital, Baltimore, to reduce ambulance bypass hours, a chronic problem resulting in $6.7 million in lost revenue annually. The goal was to reduce red alert hours per month by 50%. Three Plan-Do-Study-Act (PDSA) cycles were implemented to test change concepts. RESULTS: There was a significant reduction in red alert hours after the change initiative, with an estimated $6 million in additional hospital revenue. DISCUSSION: The integrated change model may serve as a prototype for improving complex problems in which improving organizational relationships may be as difficult as improving processes and is likely to require a significant amount of work offline. For example, this approach may be particularly helpful for improving processes that span departments or functional units such as reducing cycle times for admissions, first-dose medications, as well as in building and improving integrated delivery systems. The model awaits further testing and evolution.

Delivery of Health Care, Integrated↗
PubMed1997

Cross regulation of four GATA factors that control nitrogen catabolic gene expression in Saccharomyces cerevisiae.

Nitrogen catabolic gene expression in Saccharomyces cerevisiae has been reported to be regulated by three GATA family proteins, the positive regulators Gln3p and Gat1p/Nil1p and the negative regulator Dal80p/Uga43p. We show here that a fourth member of the yeast GATA family, the Dal80p homolog Deh1p, also negatively regulates expression of some, but not all, nitrogen catabolic genes, i.e., GAP1, DAL80, and UGA4 expression increases in a deh1 delta mutant. Consistent with Deh1p regulation of these genes is the observation that Deh1p forms specific DNA-protein complexes with GATAA-containing UGA4 and GAP1 promoter fragments in electrophoretic mobility shift assays. Deh1p function is demonstrable, however, only when a repressive nitrogen source such as glutamine is present; deh1 delta mutants exhibit no detectable phenotype with a poor nitrogen source such as proline. Our experiments also demonstrate that GATA factor gene expression is highly regulated by the GATA factors themselves in an interdependent manner. DAL80 expression is Gln3p and Gat1p dependent and Dal80p regulated. Moreover, Gln3p and Dal80p bind to DAL80 promoter fragments. In turn, GAT1 expression is Gln3p dependent and Dal80p regulated but is not autogenously regulated like DAL80. DEH1 expression is largely Gln3p independent, modestly Gat1p dependent, and most highly regulated by Dal80p. Paradoxically, the high-level DEH1 expression observed in a dal80::hisG disruption mutant is highly sensitive to nitrogen catabolite repression.

Base Sequence↗
PubMed1996

Cytomegalovirus pp65 antigenemia-guided early treatment with ganciclovir versus ganciclovir at engraftment after allogeneic marrow transplantation: a randomized double-blind study.

To determine whether cytomegalovirus (CMV) antigenemiaguided ganciclovir treatment may be as effective, may require less treatment, and thus may cause less marrow toxicity than ganciclovir administered at engraftment, 226 marrow transplant recipients were randomized at engraftment to receive placebo (antigenemia-ganciclovir group) or ganciclovir (ganciclovir group) until day 100 in a double-blind study. In patients with antigenemia of 3 or more positive cells in 2 slides and/or viremia, study drug was discontinued and ganciclovir was started for at least 3 weeks or until negative CMV antigenemia and resumed only if antigenemia recurred. More patients in the antigenemia-ganciclovir group developed CMV disease before day 100 after transplantation compared with the ganciclovir group (14% v 2.7%, P = .002). Of the 16 patients with CMV disease before day 100 in the antigenemia-ganciclovir group, 10 (8.8%) had disease before or during the first episode of antigenemia and 6 (5.3%) developed disease after discontinuation of ganciclovir. Untreated low-grade antigenemia progressed to CMV disease in 19% of patients with grade 3-4 compared with 0% of patients with grade 0-2 acute graft-versus-host disease (P = .04). There was no significant difference in CMV disease by day 180 after transplantation and thereafter. CMV-related death, transplant survival, and neutropenia were not significantly different between the groups. In the ganciclovir group, more invasive fungal infections occurred (P = .03) and more ganciclovir was used (P < .0001). Thus, delaying the start of ganciclovir until highgrade antigenemia and discontinuing ganciclovir based on negative antigenemia results in more CMV disease by day 100 than ganciclovir administered at engraftment. However, ganciclovir at engraftment is associated with more early invasive fungal infections and more late CMV disease resulting in similar survival rates.

Adolescent↗
PubMed1996

The value of isotype determination of serum antibodies against Chlamydia for the diagnosis of Chlamydia reactive arthritis.

In clinical rheumatology, the diagnosis of Chlamydia reactive arthritis is difficult because an incomplete form of the disease can closely resemble an undifferentiated seronegative mono/oligoarthritis. We investigated whether measuring specific isotypes of anti-Chlamydia antibodies in serum can improve the diagnosis, by comparing such antibody concentrations in the serum of patients with well-defined disease, i.e. Chlamydia trachomatis sexually acquired reactive arthritis (CT-SARA), with other arthritides. Antibody levels were determined by enzyme-linked immunosorbent assay (ELISA). When considering two different isotypes and their combination, the best sensitivity (63%) was obtained for IgM and/or IgA results with a specificity of 81%. The patients with CT-SARA and SARA had the highest levels of antibodies of all isotypes tested. It is concluded that, in our experimental conditions, only very high values of specific isotypes could indicate a diagnosis of Chlamydia reactive arthritis.

Adolescent↗
PubMed1996

Synovial fluid and serum antibodies against Chlamydia in different forms of arthritis: intra-articular IgA production in Chlamydia sexually acquired reactive arthritis.

Since the presence of Chlamydia has been shown in synovial fluid (SF) from some patients with Chlamydia reactive arthritis, we investigated whether anti-Chlamydia antibodies present in the joint are derived from the circulation or are locally produced. We compared titres of IgG, IgM and IgA antibodies against Chlamydia, and against a control antigen (tetanus toxoid), by an enzyme-linked immunosorbent assay (ELISA), in paired samples of serum and SF from Chlamydia trachomatis sexually acquired reactive arthritis (CT-SARA) patients and from patients with other forms of arthritis. The ratio of serum/SF IgA anti-Chlamydia antibodies was significantly decreased in CT-SARA patients. It is concluded that, in our experimental conditions, we found evidence for intra-articular production of IgA anti-Chlamydia antibodies.

Adolescent↗
PubMed1996

Gat1p, a GATA family protein whose production is sensitive to nitrogen catabolite repression, participates in transcriptional activation of nitrogen-catabolic genes in Saccharomyces cerevisiae.

Saccharomyces cerevisiae cells selectively use nitrogen sources in their environment. Nitrogen catabolite repression (NCR) is the basis of this selectivity. Until recently NCR was thought to be accomplished exclusively through the negative regulation of Gln3p function by Ure2p. The demonstration that NCR-sensitive expression of multiple nitrogen-catabolic genes occurs in a gln3 delta ure2 delta dal80::hisG triple mutant indicated that the prevailing view of the nitrogen regulatory circuit was in need of revision; additional components clearly existed. Here we demonstrate that another positive regulator, designated Gat1p, participates in the transcription of NCR-sensitive genes and is able to weakly activate transcription when tethered upstream of a reporter gene devoid of upstream activation sequence elements. Expression of GAT1 is shown to be NCR sensitive, partially Gln3p dependent, and Dal80p regulated. In agreement with this pattern of regulation, we also demonstrate the existence of Gln3p and Dal80p binding sites upstream of GAT1.

Amino Acid Sequence↗
PubMed1996

Integrated telematic support for paediatrics: a practical model.

This paper describes the benefits gained and the organizational and practical considerations involved in establishing a relatively low-cost telematic support network for paediatric care and research. It is based on a case study in north-east England, where such a system has been implemented, supporting multimedia conferencing and reference facilities, postgraduate education and management information. The role of this type of service in regional health-care provision is discussed, for paediatrics and other disciplines.

Computer Communication Networks↗
PubMed1993

Anterior mediastinal fibrosis with superior vena caval obstruction complicating the synovitis-acne-pustulosis-hyperostosis-osteomyelitis syndrome.

A syndrome of predominantly palmo-plantar pustular psoriasis associated with anterior chest wall (sternoclavicular, manubriosternal) inflammation has previously been described. In this case, a further patient is reported where chest wall involvement is complicated by anterior mediastinal fibrosis and superior vena caval obstruction.

Fibrosis↗
PubMed1991

Adhesion reformation: reduction by the use of Interceed (TC7) plus heparin.

Adhesions frequently develop after surgical procedures. Several groups have demonstrated that reduction of adhesion reformation is more difficult than reduction of adhesion formation. Previous studies have demonstrated the efficacy of Interceed (TC7) (oxidized regenerated cellulose) plus heparin in reducing adhesion formation. Adhesions were created using a previously standardized rabbit uterine horn model. After adhesiolysis, rabbits were assigned randomly to one of four groups: control, Interceed (TC7) alone, Interceed (TC7) plus 500 USP units heparin/horn, and Interceed (TC7) plus 1000 USP units heparin/horn. Adhesion reformation was evaluated 2 weeks later. Combination of the Interceed (TC7) barrier plus heparin resulted in a significant reduction of the adhesion reformation scores. It is concluded that Interceed (TC7) plus heparin is efficacious in reduction of both adhesion formation and adhesion reformation.

Animals↗
PubMed1991

Synergistic effects of INTERCEED(TC7) and heparin in reducing adhesion formation in the rabbit uterine horn model.

Surgical adjuvants are commonly employed to reduce the frequency of postoperative adhesion development after reproductive pelvic surgery. The ability of indomethacin, promethazine dexamethasone, Intralipid, progesterone, and heparin to reduce adhesion formation in combination with INTERCEED(TC7) (Johnson and Johnson Medical, Inc., New Brunswick, NJ), an absorbable barrier that alone reduces adhesion formation, was examined in a rabbit uterine horn model. A significant reduction in adhesion formation was only observed with the combination of INTERCEED(TC7) plus heparin. In addition studies, heparin delivery by intraperitoneal (IP) lavage, intravenous injection, or intra-abdominal instillation failed to demonstrate efficacy. Similarly, heparin delivery with other barriers or IP instillates (carboxymethylcellulose or 32% Dextran 70) failed to reduce adhesion formation. We conclude that INTERCEED(TC7) can be efficaciously utilized as a carrier to deliver heparin to traumatized surfaces, thereby reducing adhesion formation.

Animals↗
PubMed1990

Tropical arthritis in Papua New Guinea: a reactive arthritis.

An idiopathic, asymmetrical oligoarthritis affecting young adults is prevalent in the tropical regions of Africa, Asia and Melanesia. A serological study was undertaken in 23 consecutive patients with polyarthritis. Each patient was assigned two paired control subjects. A standardized history, physical examination and investigations were performed. Acute and convalescent sera were examined for evidence of recent infection. The presence of HLA-B27 was determined. Twelve (52%) of the 23 patients had more than one of the clinical features of a reactive arthritis. No serological evidence was found of acute infection with viruses (arboviruses, enteroviruses, mumps, rubella, adenoviruses, Epstein-Barr virus and hepatitis B), Chlamydia, Mycoplasma, Yersinia or syphilis. HLA-B27 was found in 14 (61%) of the 23 patients in contrast with in seven (17%) of the 41 control subjects (P less than 0.001). In two patients with HLA-B27, diagnostic titres of antibodies to Campylobacter jejuni-Campylobacter coli indicated recent infection. The presence of HLA-B27 antigen was significantly (P less than 0.05) associated with the presence of the clinical features of reactive arthritis. This study suggests that "tropical arthritis" commonly is a reactive arthritis that is associated with the presence of HLA-B27.

Acute Disease↗
PubMed1990

A biomechanical study of tendon adhesion reduction using a biodegradable barrier in a rabbit model.

Adhesion formation associated with tendon surgery is a widespread problem in which a healing tendon becomes adherent via scar tissue to surrounding structures such as bone, muscle, skin, tendon sheath, or other tendons. A model is described in which adhesions were generated reproducibly between the plantaris and Achilles tendons of the rabbit using a partial tenotomy, a Bunnel suture, and immobilization. Using this model, the effect of an absorbable barrier, INTERCEED (TC7), on adhesion formation was investigated. This material, which is a fabric comprised of oxidized regenerated cellulose, was found to diminish significantly the extent and severity of intertendinous adhesions, assessed both mechanically and histologically. No evidence of a foreign body reaction was observed.

Animals↗