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Biomedical subjects

K Cunningham

Publications and source records attributed to K Cunningham.

At least 19 recordsLinked to original sources
PubMed2001

Relationship between acute morphine and the course of PTSD in children with burns.

OBJECTIVE: To investigate the relationship between the dose of morphine administered during a child's hospitalization for an acute burn and the course of posttraumatic stress disorder (PTSD) symptoms over the 6-month period following discharge from the hospital. METHOD: Twenty-four children admitted to the hospital for an acute burn were assessed twice with the Child PTSD Reaction Index: while in the hospital and 6 months after discharge. The Colored Analogue Pain Scale was also administered during the hospitalization. All patients received morphine while in the hospital. The mean dose of morphine (mg/kg/day) was calculated for each subject through chart review. RESULTS: The Pearson product moment correlation revealed a significant association between the dose of morphine received while in the hospital and a 6-month reduction in PTSD symptoms. Children receiving higher doses of morphine had a greater reduction in PTSD symptoms over 6 months. CONCLUSIONS: This study suggests the possibility that acute treatment with morphine can secondarily prevent PTSD. This result is discussed in terms of the possible effect of morphine on fear conditioning and the consolidation of traumatic memory.

Adolescent↗
PubMed2001

Estimates of the health risk reductions associated with attainment of alternative particulate matter standards in two U.S. cities.

As part of its periodic re-evaluation of particulate matter (PM) standards, the U.S. Environmental Protection Agency estimated the health risk reductions associated with attainment of alternative PM standards in two locations in the United States with relatively complete air quality data: Philadelphia and Los Angeles. PM standards at the time of the analysis were defined for particles of aerodynamic diameter less than or equal to 10 microm, denoted as PM-10. The risk analyses estimated the risk reductions that would be associated with changing from attainment of the PM-10 standards then in place to attainment of alternative standards using an indicator measuring fine particles, defined as those particles of aerodynamic diameter less than or equal to 2.5 microm and denoted as PM-2.5. Annual average PM-2.5 standards of 12.5, 15, and 20 microg/m3 were considered in various combinations with daily PM-2.5 standards of 50 and 65 microg/m3. Attainment of a standard or set of standards was simulated by a proportional rollback of "as is" daily PM concentrations to daily PM concentrations that would just meet the standard(s). The predicted reductions in the incidence of health effects varied from zero, for those alternative standards already being met, to substantial reductions of over 88% of all PM-associated incidence (e.g., in mortality associated with long-term exposures in Los Angeles, under attainment of an annual standard of 12.5 microg/m3). Sensitivity analyses and integrated uncertainty analyses assessed the multiple-source uncertainty surrounding estimates of risk reduction.

Air Pollutants↗
PubMed2001

Some considerations concerning multimedia-multipollutant risk assessment methodology: use of epidemiologic data for non-cancer risk assessment in Russia.

The highly industrialized small town of Verkhnyaya Pyshma (in the Urals region of Russia) was chosen as the site of a multimedia-multipollutant risk assessment using the U.S. Environmental Protection Agency methodology. The assessment was based on routine environmental pollution monitoring data for ambient air, soils, drinking water, and food, and the international environmental epidemiology literature. Using an a priori set of the preliminary health-based criteria, we selected nine pollutants for risk assessment: total suspended particles (TSP), sulfur dioxide, nitrogen dioxide, benzo(a)pyrene (BaP), ammonia arsenic, copper, cadmium, and lead. We used dose-response functions derived from epidemiologic studies to assess individual and population risks for TSP, SO2, NO2, As, Cd, and Pb. We assessed both cancer (for BaP, As, and Cd) and non-cancer (for all the chosen pollutants but BaP) responses, but in this paper we discuss only the assessments of noncarcinogenic risks due to TSP, SO2, NO2, Pb, and Cd as examples of how the quantitative estimates of health effects can be produced by using a risk function approach. We also schematically present a modified conceptual model of multimedia-multipollutant risk assessment taking into account the experience gained with this study.

Adolescent↗
PubMed2000

CIKS, a connection to Ikappa B kinase and stress-activated protein kinase.

Pathogens, inflammatory signals, and stress cause acute transcriptional responses in cells. The induced expression of genes in response to these signals invariably involves transcription factors of the NF-kappaB and AP-1/ATF families. Activation of NF-kappaB factors is thought to be mediated primarily via IkappaB kinases (IKK), whereas that of AP-1/ATF can be mediated by stress-activated protein kinases (SAPKs; also named Jun kinases or JNKs). IKKalpha and IKKbeta are two catalytic subunits of a core IKK complex that also contains the regulatory subunit NEMO (NF-kappaB essential modulator)/IKKgamma. The latter protein is essential for activation of the IKKs, but its mechanism of action is not known. Here we describe the molecular cloning of CIKS (connection to IKK and SAPK/JNK), a previously unknown protein that directly interacts with NEMO/IKKgamma in cells. When ectopically expressed, CIKS stimulates IKK and SAPK/JNK kinases and it transactivates an NF-kappaB-dependent reporter. Activation of NF-kappaB is prevented in the presence of kinase-deficient, interfering mutants of the IKKs. CIKS may help to connect upstream signaling events to IKK and SAPK/JNK modules. CIKS could coordinate the activation of two stress-induced signaling pathways, functions reminiscent of those noted for tumor necrosis factor receptor-associated factor adaptor proteins.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Moving beyond the illness: factors contributing to gaining and maintaining employment.

The work presented here, exploratory in nature, uses a comparative and qualitative approach to understand the factors associated with the ability of individuals with severe and persistent mental illness to successfully gain and maintain employment. Based on open-ended interviews with individuals in an Assertive Community Treatment (ACT) program, we compare the experiences of those who have been successful gaining and maintaining employment, with those who have been successful gaining but not maintaining work, and those who have been unsuccessful gaining employment. The three groups seemed to differ in three significant ways: (1) in the ways the individuals talked about their illness, (2) in the ways the individuals talked about work, and (3) in the strategies they described for coping with bad days. In each of these areas individuals' awareness of and attitude toward their illness was significant. The findings have clear implications for agencies working to help people with severe and persistent mental illness obtain and maintain employment.

Adult↗
PubMed2000

A DNase I hypersensitive site near the murine gamma1 switch region contributes to insertion site independence of transgenes and modulates the amount of transcripts induced by CD40 ligation.

Several cis-acting elements regulate the expression of germline transcripts of heavy chain constant region genes and their subsequent switch recombination. To study such elements in the murine gamma1 gene, we have utilized a transgenic approach. In this study we focused on a DNase I hypersensitive site (termed 'Site II') that lies about 2 kb 3' of the gamma1 promoter region and I exon, just 5' to the gamma1 switch region. We have reported that gamma1 transgenes with Site II display the characteristics of a locus control region (LCR) in that they are insertion site independent and copy number dependent. For the present study we prepared six lines of transgenic mice that have the promoter region and I exon, but lack Site II. Expression of RNA from gamma1 transgenes that lack Site II is not correlated with transgene copy number; expression is insertion site dependent. This result indicates that DNase hypersensitive Site II is an important part of the LCR-like elements in the murine gamma1 gene. RNA expression from the gamma1 transgenes that lack Site II is inducible by IL-4 and by CD40 ligation. However, the induction of transgenic RNA expression by CD40 ligation is greater than expected, suggesting that elements within Site II participate in negative regulation of the amount of germline transcripts after CD40 ligation.

Animals↗
PubMed2000

Airbag associated fatal head injury: case report and review of the literature on airbag injuries.

Airbags have been shown to significantly reduce mortality and morbidity in motor vehicle crashes. However, the airbag, like the seat belt, produces its own range of injuries. With the increasing use of airbags in the UK, airbag associated injuries will be seen more often. These are usually minor, but in certain circumstances severe and fatal injuries result. Such injuries have been described before in the medical literature, but hitherto most reports have been from North America. This is the first case report from the UK of serious injury due to airbag deployment and describes the case of a driver who was fatally injured when her airbag deployed in a moderate impact frontal collision where such severe injury would not normally have been anticipated. The range of airbag associated injuries is described and predisposing factors such as lack of seat belt usage, short stature, and proximity to airbag housing are discussed. The particular dangers airbags pose to children are also discussed.

Accidents, Traffic↗
PubMed1999

Distinct activities of p52/NF-kappa B required for proper secondary lymphoid organ microarchitecture: functions enhanced by Bcl-3.

Mice rendered deficient in p52, a subunit of NF-kappa B, or in Bcl-3, an I kappa B-related regulator that associates with p52 homodimers, share defects in the microarchitecture of secondary lymphoid organs. The mutant mice are impaired in formation of B cell follicles and are unable to form proper follicular dendritic cell (FDC) networks upon antigenic challenge. The defects in formation of B cell follicles may be attributed, at least in part, to impaired production of the B lymphocyte chemoattractant (BLC) chemokine, possibly a result of defective FDCs. The p52- and Bcl-3-deficient mice exhibit additional defects within the splenic marginal zone, including reduced numbers of metallophilic macrophages, reduced deposition of the laminin-beta 2 chain and impaired expression of a mucosal addressin marker on sinus-lining cells. Whereas p52-deficient mice are severely defective in all of these aspects, Bcl-3-deficient mice are only partially defective. We determined that FDCs or other non-hemopoietic cells that underlie FDCs are intrinsically impaired in p52-deficient mice. Adoptive transfers of wild-type bone marrow into p52-deficient mice failed to restore FDC networks or follicles. The transfers did restore metallophilic macrophages to the marginal zone, however. Together, the results suggest that p52 carries out functions essential for a proper splenic microarchitecture in both hemopoietic and non-hemopoietic cells and that Bcl-3 is important in enhancing these essential activities of p52.

Adjuvants, Immunologic↗
PubMed1998

Potential regulatory elements for germline transcription in or near murine Sgamma1.

We were interested in identifying cis-acting elements that regulate germline transcription and switch recombination of heavy chain genes. The murine gamma1 heavy chain gene includes two DNase I hypersensitive sites, which may represent protein:DNA interactions important for germline transcription and switch recombination. One DNase hypersensitive site is at the promoter/I exon boundary (termed 'Site I'); we localized a second pair of DNase hypersensitive sites to just 5' of the Sgamma1 region (termed 'Site II'). The DNA region of hypersensitive Site II includes a NF-kappaB/Rel binding site and a STAT6 binding site. It is noteworthy that NF-kappaB and STAT6 are induced by the same agents (CD40 ligation and IL-4 respectively) that stimulate germline transcription and switch recombination of the murine gamma1 gene. Transgenes with the gamma1 promoter region (DNase hypersensitive Site I), Igamma1 and DNase I hypersensitive Site II expressed germline transcripts with correct regulation, including IL-4 inducibility. However, the level of stable transcripts produced by the transgenes was much lower than that of the endogenous gamma1 gene, a complete 17 kb gamma1 transgene or a derivative of the 17 kb gamma1 transgene that lacked most of Cgamma1. The promoter/Igamma1/Site II transgenes lacked Sgamma1 and we found that gamma1 transgenes that lacked only Sgamma1 also expressed germline transcripts with proper regulation, but at a low level. This suggested that the Sgamma1 region includes positive elements for regulation of the amount of germline transcripts.

Animals↗
PubMed1998

Germline transcription and recombination of a murine VDJmudeltagamma1 transgene.

To investigate the regulation of Ig switch recombination, we have constructed mice with a 56 kb VDJmudeltagamma1 transgene. This transgene included an anti-nitrophenyl VDJ segment, Smu, Cmu, Cdelta, Igamma1, Sgamma1, Cgamma1 and the Cgamma1 membrane exons from the murine Igh(a) haplotype. Two founder lines were produced, with very similar characteristics. Transgenic B cells expressed normal amounts of Cmu (which is >95% transgenic), Cdelta and other cell surface markers, and normal amounts of VDJ and Cmu RNA. Gamma1 germline transcription of the transgenes is properly regulated since stable transcripts were not expressed in B cells treated with lipopolysaccharide (LPS) alone, nor in thymus or non-lymphoid tissues, but were expressed after treatment of B cells with LPS + IL-4 or CD40L + IL-4. B cells from both lines of transgenic mice expressed transgenic gamma1a after in vitro culture with CD40L + IL-4, but not after culture with CD40L alone. However, the CD40L + IL-4 induced IgG1 precursor frequency is much lower for VDJmudeltagamma1 transgenic B cells (1:240-760) than for non-transgenic B cells (1:9). Analysis of DNA from transgenic hybridomas indicated that switch recombination can take place in switch (S) regions, but can also take place outside S regions. These results indicate that targeting of switch recombinase to S regions must include regulation beyond the S regions themselves and correct germline transcription. This additional regulation might include cis-acting elements or appropriate spacing or arrangement of the recombining elements.

Animals↗
PubMed1997

Informed consent from whom?

To obtain legally safe informed consent requires that the patient has a 'substantial understanding' of the proposed procedure and that the doctor obtaining the informed consent has sufficient knowledge to explain the nature of the procedure to the patient. In this paper we have shown that significant misunderstanding exists among non-specialist junior doctors of certain common orthopaedic procedures and conditions. Junior doctors often lack sufficient technical training to fully inform their patients and thus meet legal requirements. The implications of this are that the onus falls even more on specialists to ensure that their patients receive a more detailed explanation of the proposed intervention.

Arthroscopy↗
PubMed1997

Enhanced ex vivo cosedimentation of high molecular weight neurofilament protein (NFH) with microtubules following in vivo aluminum chloride exposure: inhibition of dephosphorylation-dependent dissociation.

We have investigated the effect of acute in vivo aluminum exposure on the subsequent ex vivo cross-linking of the high molecular weight neurofilament protein (NFH) with polymerized microtubules. Young adult female New Zealand white rabbits were inoculated intracisternally with 1000 micrograms of AlCl3 in 0.9% NaCl or with 0.9% NaCl alone, and killed 48 hours later. Following isolation of a cytoskeletal-enriched protein fraction from the cervical spinal cord, NFH was purified by either electroelution or column chromatography. Tubulin was isolated from New Zealand white rabbit brains by repeated temperature-dependent polymerization and depolymerization, purified over phosphocellulose, and cosedimented with either phosphorylated or dephosphorylated NFH. Following incubation for 30 minutes at 32 degrees C with tubulin in the presence of 20 microM Taxol, 1.0 mM MgCl2 and 1.0 mM GTP, the insoluble pellet containing NFH/microtubules was isolated. Both the pellet and supernatent were fractionated by SDS.PAGE and the amount of NFH present quantified by transmission densitometry following silver-staining. Results were identical regardless of the technique utilized for the purification of NFH. Control NFH preferentially cosedimented with microtubules when in the fully phosphorylated isoform, but remained in the soluble fraction following dephosphorylation. Phosphorylated NFH derived from AlCl3-inoculated rabbits demonstrated similar binding characteristics to control NFH, but following exhaustive dephosphorylation, exhibited a 4.5 fold induction of NFH/microtubule binding (p = 0.0314). Incubating dephosphorylated control NFH with microtubules in the presence of increasing concentrations of AlCl3 failed to induce similar cosedimentation. These experiments suggest that phosphorylation promotes NFH cross-linking to microtubules. In addition, the phosphorylation/dephosphorylation dependent regulation of NFH cross-linking to microtubules is disrupted following in vivo AlCl3 exposure by a mechanism that s independent of NFH/Al3+ binding.

Aluminum Chloride↗
PubMed1997

Ovarian abscess 15 months after vaginal hysterectomy. A case report.

BACKGROUND: Ovarian abscess is a primary infection of ovarian parenchyma. Since 1869, only 44 cases after vaginal hysterectomy have been reported in the medical literature. The pathophysiology of bacterial infection in these cases is different from the traditional ascending mechanism. CASE: A 28-year-old woman presented with complaints of lower abdominal pain and fever 15 months after transvaginal hysterectomy. Her white blood cell count was 22,700/mm3, with 90% neutrophils. Bimanual examination revealed a tender mass in the cul-de-sac, and computed tomography showed a large, multiloculated pelvic mass. Laparotomy, pathologic examination and microbiologic study confirmed the diagnosis of ovarian abscess. CONCLUSION: Our case represents another rare posthysterectomy ovarian abscess. Most of these cases were managed by surgery and antibiotic treatment.

Abscess↗
PubMed1996

A new form of polyagglutination related to Cad.

Four phenotypes of Cad (Cad 1-4) have been characterized by a continuum of polyagglutinability and reactivity with lectins, with the strongest Cad+ red blood cells (RBCs) being polyagglutinable because of the presence of anti-Cad (anti-Sda) in most normal sera. Over a period of 7 years, a French male blood donor's RBCs demonstrated polyagglutinability with 50 percent to 70 percent of normal adult sera. The reactivity was characteristic of anti-Sda (refractile agglutination at 4 degrees C, 20 degrees C, 37 degrees C, and anti-human globulin test), and was inhibitable by two examples of Sd(a+) urine, but not by Sd(a-) urine or dialysate from Sd(a+) urine. The donor's RBCs reacted 1+ with Glycine max, but did not react with Dolichos biflorus, Leonurus cardiaca, Salvia horminum, or Arachis hypogaea. The first four of these lectins were reactive with five of five Cad+ RBCs, including one example of Cad 4 RBCs. Polybrene(R) aggregated the donor RBCs. Dilutions of nine samples of anti-Sda reacted more strongly with the donor RBCs than with normal RBCs. Even though lectin studies failed to classify this donor's RBCs as Cad, the persistent polyagglutinability and serologic characteristics are consistent with Cad and demonstrate the heterogeneity of this antigen.

Journal Article↗
PubMed1996

Effects of gentle human touch on preterm infants: pilot study results.

A pilot study was conducted to evaluate the effects of gentle human touch (GHT) provided for 15 minutes a day to preterm infants from day 7 to day 12 of life. The study suggested that GHT has no adverse effects on the oxygen saturation or heart rate levels of small preterm infants and that GHT has a soothing effect as evidenced by decreased levels of active sleep, motor activity, and behavioral distress. These results can provide NICU nurses with a basis for guiding parents in their early interactions with preterm infants in the NICU.

Female↗
PubMed1995

Precision and accuracy of clinical and radiological signs in premature infants at risk of patent ductus arteriosus.

OBJECTIVE: To determine the precision (interobserver agreement) and accuracy (agreement with criterion standard) of clinical and radiological signs in premature infants at risk of patent ductus arteriosus (PDA) with left-to-right shunting. DESIGN: Masked comparison of clinical and radiological examination with Doppler flow echocardiography (criterion standard). SETTING: Neonatal intensive care unit. PATIENTS: One hundred infants with birth weights less than 1750 g were studied once between days 3 and 7 of life. A third of the cohort was intubated at the time of study. INTERVENTION: Five independent observers noted the presence or absence of an increased pulse volume, an active precordium, a heart murmur, a cardiothoracic ratio greater than 60%, increased pulmonary vascular markings on a concurrent chest x-ray film, and a relative increase of the cardiothoracic ratio compared with that from the previous chest x-ray film. Pulsed and color flow Doppler echocardiography was performed within 4 hours. All 100 tapes were reviewed by a second pediatric cardiologist. RESULTS: Twenty-three infants had a PDA with left-to-right shunting. The precision of clinical signs was modest, with average kappa values of 0.15 for pulse volume, 0.32 for precordium, and 0.41 for murmur. Pulse quality (43%) and murmur (42%) had the highest mean sensitivities. Corresponding specificities were 74% for pulse volume and 87% for murmur. The combination of a cardiac murmur with an abnormal pulse volume had the highest positive predictive value (77%). The radiological examination did not improve the observers' ability to distinguish between patients with and without PDA. CONCLUSIONS: The precision and accuracy of clinical and radiological signs of a PDA with left-to-right shunting are unsatisfactory. Therefore, Doppler flow echocardiography is required to diagnose PDA confidently in preterm infants between days 3 and 7 of life.

Ductus Arteriosus, Patent↗
PubMed1995

Elevation in anti-Proteus antibodies in patients with rheumatoid arthritis from Bermuda and England.

OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) from Bermuda and England have an increased anti-Proteus antibody titer when compared to healthy Bermudian and English controls, and to ascertain whether any increase in antibody titer is specific by testing 4 other microbes, Escherichia coli and 3 normal anaerobic bowel bacteria. METHODS: Antibody titers were measured by ELISA and indirect immunofluorescence (IIFA) under coded conditions. RESULTS: Elevated titers of anti-Proteus antibodies were demonstrated in 34 patients with active RA from Bermuda when compared to 33 healthy Bermudian controls by ELISA (p < 0.001) and IIFA (p < 0.001). An elevation of anti-Proteus antibodies was also observed in 34 patients with RA from England when compared to 30 healthy English controls again by ELISA (p < 0.001). A similar antibody elevation in 31 patients with RA from England was observed when compared to 30 healthy controls when measured by IIFA (p < 0.001). However, there was no significant elevation in antibody titers against E. coli or the 3 normal bowel flora isolates in the patients with RA from both countries compared to their respective controls, when measured by ELISA. CONCLUSION: A specific elevation in the immune response to Proteus mirabilis has been demonstrated in patients with RA from both Bermuda and England. However, this study cannot distinguish between antibody association with disease per se and association with disease activity. The role of Proteus in RA and the effect of anti-Proteus therapy in patients with RA merits further study.

Adult↗