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Biomedical subjects

C Kirkpatrick

Publications and source records attributed to C Kirkpatrick.

At least 19 recordsLinked to original sources
PubMed2003

Assessment of adrenal suppression from two new dry powder inhaler formulations of budesonide delivered by Clickhaler compared with the Pulmicort Turbuhaler.

Assessment of adrenal suppression via systemic cortisol levels provides an indirect measure of the lung delivery of inhaled corticosteroids. This randomized, placebo-controlled, double-blind, double-dummy crossover study compared urinary and plasma cortisol levels in healthy adult volunteers following single 1,000-microg doses of budesonide from two multiple dose dry powder inhalers (DPIs). Two new formulations of budesonide (lactose and PassCal) delivered from the Clickhaler were compared with Pulmicort from the Turbuhaler. An open dose (2,000 microg) of Pulmicort Turbuhaler was included to validate the experimental model. Overnight (22:00-07:00 h) and early morning (07:00-08:00 h) urine and 08:00 h plasma samples were collected after each treatment and cortisol levels analyzed by radioimmunoassay. Combined overnight and early morning urinary cortisol values for PassCal Clickhaler and Pulmicort Turbuhaler (1,000 microg) were statistically significantly lower than placebo (p < 0.05). The lactose budesonide Clickhaler showed a non-significant urinary cortisol reduction compared with placebo. Differences between the three 1,000-microg budesonide treatments were not significant. The Pulmicort Turbuhaler 2,000 microg showed significant urinary cortisol suppression compared with placebo. Plasma cortisol showed similar effects, with significance between the two Pulmicort doses. These results suggest that adrenal suppression can be used to assess the pulmonary bioavailability of different formulation.

Adrenal Glands↗
PubMed2002

Successful medical management of multifocal psoas abscess following cesarean section: report of a case and review of the literature.

The psoas abscess is a rare complication in obstetric and gynaecology. Two types of psoas abscess are recognized. The primary psoas abscess is generally following haematogenous dissemination of an infectious agent and the source is usually occult. The most frequently isolated pathogen is Staphylococcus aureus. On the other hand, the secondary abscess is the result of local extension of an infectious process near the psoas muscle. We report the case of a patient who develops a bacteremia from an infected cesarean section wound. The complications were thigh and psoas abscesses with left sacroiliitis. Medical management with prolonged antibiotherapy permit clinical, biological and radiological improvement. Although it required a long hospital stay, medical treatment alone was effective. More experience is required to determine which therapeutic option: medical treatment and/or surgery, is the best choice for this type of complication.

Adult↗
PubMed2002

[Medically assisted reproduction in couples carrying the human immunodeficiency virus].

Today, in developed countries, many HIV-infected people remain in good health thanks to antiviral medication, and a growing number of them want to have children. The benefit of resorting to assisted procreation and the contamination prevention strategies, throughout pregnancy, are summarized as well as the changes in ethical considerations. The balance between the importance of the message of prevention and the benefit for patients of being assisted in their desire for a child, has evolved towards a growing interest for medical intervention in order to avoid the risks of spontaneous conception outside health care structures. We are presenting the medical structure adapted at Erasme hospital and the 38 first requests taken into account by our pluridisciplinary team. This approach, which is coherent from a scientific point of view, respects both the autonomy of people, carrying HIV as well as the essential interest of the child, in being born uninfected, and also has the enormous advantage of allowing access to parenthood without destroying the consistency and coherence of the message of prevention of sexual contamination.

Carrier State↗
PubMed2002

[The gynecology-obstetrics department].

The scientific and clinical activities of the Department of Obstetrics and Gynaecology have involved the three main subdivisions: the gynecological surgery, the obstetrics and fetal medicine, the endocrinology and the reproductive medicine. Minimal invasive surgery including laser assisted laparoscopy or robotic assisted surgery has been particularly developed. Endometriosis, a frequent and sometimes particularly invasive disease, and oncologic surgeries have been developed in collaboration with the digestive surgery department. The department has also contributed to the comprehension and treatment of prenatal pathologies such as premature labor and deliveries or the gestational diabetes. The department has supported the development of techniques to study the fetal well-being in utero: the prenatal echography, the chorionic villous sampling, the amniotic puncture or the cordocentesis for prenatal genetic diagnosis or fetal infectious contaminations, the CMV transmission more specifically. In endocrinology and reproductive medicine, the department has mainly developed the in vitro fertilization techniques. The prolonged embryo culture, the study of preimplantation embryo metabolism, the preimplantation genetic diagnosis and the cryopreservation of ovarian fragments to preserve fertility in women undergoing oncologic treatments represent the more recent developed topics. Finally, the security of viral transmission in assisted procreation and the treatment of these patients with chronic viral diseases (Hepatitis C or HIV) are another domain with important scientific activity.

Belgium↗
PubMed2001

Fifteen years of drug information in Christchurch Hospital.

AIM: To determine changes in numbers, demography and type of questions posed to the drug information service (DIS) at Christchurch Hospital over the last fifteen years. METHODS: The database of the DIS was used to retrieve data for one-year periods including the period of establishment in 1985/1986, 1993/1994 and 1999/2000. RESULTS: The number of questions per month increased from 26 in 1985/1986 to 284 in 1999/2000. The majority of questions have related to adverse drug reactions, contraindications/precautions, drug selection, interactions, and administration/dosage. Questions on drug interactions showed the greatest relative increase, from 8% to 19% of all questions. A disproportionate increase in requests came from primary care, which provided 14% of questions in 1985/1986 and 38% in 1999/2000. Computer databases are the major resource used currently whereas journal articles and textbooks dominated in 1985/1986. CONCLUSIONS: There has been a marked increase in use of the DIS despite a relatively constant population base. This may reflect an increased awareness of both the availability of the service and recognition of the complexity of medicines. The computer database is a useful reference source, decreasing repetition of search pathways and allowing audit to assist in the ongoing improvement of the service.

Data Interpretation, Statistical↗
PubMed2001

Cadherin sequences that inhibit beta-catenin signaling: a study in yeast and mammalian cells.

Drosophila Armadillo and its mammalian homologue beta-catenin are scaffolding proteins involved in the assembly of multiprotein complexes with diverse biological roles. They mediate adherens junction assembly, thus determining tissue architecture, and also transduce Wnt/Wingless intercellular signals, which regulate embryonic cell fates and, if inappropriately activated, contribute to tumorigenesis. To learn more about Armadillo/beta-catenin's scaffolding function, we examined in detail its interaction with one of its protein targets, cadherin. We utilized two assay systems: the yeast two-hybrid system to study cadherin binding in the absence of Armadillo/beta-catenin's other protein partners, and mammalian cells where interactions were assessed in their presence. We found that segments of the cadherin cytoplasmic tail as small as 23 amino acids bind Armadillo or beta-catenin in yeast, whereas a slightly longer region is required for binding in mammalian cells. We used mutagenesis to identify critical amino acids required for cadherin interaction with Armadillo/beta-catenin. Expression of such short cadherin sequences in mammalian cells did not affect adherens junctions but effectively inhibited beta-catenin-mediated signaling. This suggests that the interaction between beta-catenin and T cell factor family transcription factors is a sensitive target for disruption, making the use of analogues of these cadherin derivatives a potentially useful means to suppress tumor progression.

Amino Acid Sequence↗
PubMed2001

Acetate and formate stress: opposite responses in the proteome of Escherichia coli.

Acetate and formate are major fermentation products of Escherichia coli. Below pH 7, the balance shifts to lactate; an oversupply of acetate or formate retards growth. E. coli W3110 was grown with aeration in potassium-modified Luria broth buffered at pH 6.7 in the presence or absence of added acetate or formate, and the protein profiles were compared by two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Acetate increased the steady-state expression levels of 37 proteins, including periplasmic transporters for amino acids and peptides (ArtI, FliY, OppA, and ProX), metabolic enzymes (YfiD and GatY), the RpoS growth phase regulon, and the autoinducer synthesis protein LuxS. Acetate repressed 17 proteins, among them phosphotransferase (Pta). An ackA-pta deletion, which nearly eliminates interconversion between acetate and acetyl-coenzyme A (acetyl-CoA), led to elevated basal levels of 16 of the acetate-inducible proteins, including the RpoS regulon. Consistent with RpoS activation, the ackA-pta strain also showed constitutive extreme-acid resistance. Formate, however, repressed 10 of the acetate-inducible proteins, including the RpoS regulon. Ten of the proteins with elevated basal levels in the ackA-pta strain were repressed by growth of the mutant with formate; thus, the formate response took precedence over the loss of the ackA-pta pathway. The similar effects of exogenous acetate and the ackA-pta deletion, and the opposite effect of formate, could have several causes; one possibility is that the excess buildup of acetyl-CoA upregulates stress proteins but excess formate depletes acetyl-CoA and downregulates these proteins.

Acetates↗
PubMed2001

Sacral nerve stimulation in patients with chronic intractable pelvic pain.

PURPOSE: Transforamenal sacral nerve stimulation with an implantable neuroprosthetic device has been shown to benefit patients with chronic voiding dysfunction. In this study we measured the effectiveness of sacral nerve stimulation in 10 patients with chronic intractable pelvic pain. MATERIALS AND METHODS: After successful percutaneous trial stimulation, a neuroprosthetic sacral nerve stimulation device was surgically implanted in 10 patients with chronic intractable pelvic pain. Leads were placed in the S3 and S4 foramen in 8 and 2 cases, respectively. Patients were evaluated throughout the study using a patient pain assessment questionnaire on a scale of 0-absent to 5-excruciating pain. Pain was assessed at baseline, during test stimulation, and 1, 3 and 6 months after surgical lead implantation. An additional long-term assessment was done at a median followup of 19 months. RESULTS: Of the 10 patients with the implant 9 had a decrease in the severity of the worst pain compared to baseline at a median followup of 19 months. The number of hours of pain decreased from 13.1 to 6.9 at the same followup interval. There was also an average decrease in the rate of pain from 9.7 at baseline to 4.4 on a scale of 10-always to 0-never having pain. At a median of 19 months 6 of 10 patients reported significant improvement in pelvic pain symptomology. CONCLUSIONS: These data imply that transforamenal sacral nerve stimulation can have beneficial effects on the severity and frequency of chronic intractable pelvic pain. Future clinical studies are necessary to determine the long-term effectiveness of this therapy.

Adult↗
PubMed2000

pH-dependent protein profiles of Helicobacter pylori analyzed by two-dimensional gels.

BACKGROUND: Helicobacter pylori survives transient exposure to extreme acid prior to adherence and growth on the gastric epithelium at neutral pH. MATERIALS AND METHODS: The effect of pH stress on protein profiles of H. pylori was observed using two-dimensional gel electrophoresis (2-D gels). H. pylori 26695 was grown microaerobically in tryptone-yeast extract broth, 3% fetal bovine serum. Growth in acid alkalinized the medium, whereas growth in base caused acidification. For 2-D gel analysis of protein profiles, cultures were grown in media buffered at pH 5.7 and at pH 7.5. RESULTS: Under all pH conditions, the most abundant proteins observed were the urease structural subunit UreB and the chaperonin GroEL. Growth in acid significantly increased the abundance of UreB. Thus, urease expression is not completely constitutive, as reported previously, but shows regulation by pH. Another protein observed only at low pH was identified as mammalian apolipoprotein A-I, possibly taken up by H. pylori from bovine serum in the growth medium. This finding, if confirmed, suggests that uptake of high-density lipoprotein from the human host may facilitate acquisition of cholesterol, required for formation of the unique cholesteryl glucosides in the membrane of H. pylori. In growth above pH 7, three stress proteins were induced: GroES (HspA), GroEL (HspB), and the antioxidant AhpC homolog TsaA. In addition, N-terminal sequence analysis identified five additional proteins that had not previously been reported on 2-D gels of H. pylori (FMN, SodB, TrxB, TsaA, and Tsr). CONCLUSIONS: In summary, our 2-D gel study reveals expression of several proteins dependent on growth pH.

Bacterial Proteins↗
PubMed2000

A pilot study with simvastatin and folic acid/vitamin B12 in preparation for the Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH).

BACKGROUND AND AIM: This study was conducted in preparation for the Study Evaluating Additional Reduction in Cholesterol and Homocysteine (SEARCH). SEARCH is a 12,000 patient 2X2 factorial study in post-myocardial infarction patients that will compare simvastatin 20 mg with simvastatin 80 mg to evaluate whether greater LDL-C reductions with simvastatin provide greater coronary event reductions. SEARCH will also test the hypothesis that lowering plasma homocysteine with folic acid and vitamin B12 will reduce coronary events. This pilot study was performed to determine whether any clinically meaningful interaction between simvastatin and folic acid/vitamin B12 exists. METHODS AND RESULTS: Following a 2-week diet/placebo run-in period, 141 patients with primary hypercholesterolaemia were randomised to one of three treatments for 6 weeks: 80 mg/day simvastatin and 2 mg folic acid/0.8 mg vitamin B12 daily (combination group); or 80 mg/day simvastatin and placebo vitamins (simvastatin alone group); or 2 mg folic acid/0.8 mg vitamin B12 daily and placebo simvastatin (vitamins alone group). The combination group and simvastatin alone group experienced similar serum lipid changes with reductions in LDL-cholesterol of 55.2% and 51.5% respectively. The combination group and vitamins alone group experienced similar homocysteine lowering with reductions in homocysteine of 25.3% and 23.1% respectively. All therapies were well tolerated. CONCLUSIONS: There was no detectable antagonistic effect when simvastatin and folic acid/vitamin B12 were administered concomitantly.

Cholesterol↗
PubMed1999

Drosophila APC2 is a cytoskeletally-associated protein that regulates wingless signaling in the embryonic epidermis.

The tumor suppressor adenomatous polyposis coli (APC) negatively regulates Wingless (Wg)/Wnt signal transduction by helping target the Wnt effector beta-catenin or its Drosophila homologue Armadillo (Arm) for destruction. In cultured mammalian cells, APC localizes to the cell cortex near the ends of microtubules. Drosophila APC (dAPC) negatively regulates Arm signaling, but only in a limited set of tissues. We describe a second fly APC, dAPC2, which binds Arm and is expressed in a broad spectrum of tissues. dAPC2's subcellular localization revealed colocalization with actin in many but not all cellular contexts, and also suggested a possible interaction with astral microtubules. For example, dAPC2 has a striking asymmetric distribution in neuroblasts, and dAPC2 colocalizes with assembling actin filaments at the base of developing larval denticles. We identified a dAPC2 mutation, revealing that dAPC2 is a negative regulator of Wg signaling in the embryonic epidermis. This allele acts genetically downstream of wg, and upstream of arm, dTCF, and, surprisingly, dishevelled. We discuss the implications of our results for Wg signaling, and suggest a role for dAPC2 as a mediator of Wg effects on the cytoskeleton. We also speculate on more general roles that APCs may play in cytoskeletal dynamics.

Actins↗
PubMed1999

Identification of APC2, a homologue of the adenomatous polyposis coli tumour suppressor.

The adenomatous polyposis coli (APC) tumour-suppressor protein controls the Wnt signalling pathway by forming a complex with glycogen synthase kinase 3beta (GSK-3beta), axin/conductin and betacatenin. Complex formation induces the rapid degradation of betacatenin. In colon carcinoma cells, loss of APC leads to the accumulation of betacatenin in the nucleus, where it binds to and activates the Tcf-4 transcription factor (reviewed in [1] [2]). Here, we report the identification and genomic structure of APC homologues. Mammalian APC2, which closely resembles APC in overall domain structure, was functionally analyzed and shown to contain two SAMP domains, both of which are required for binding to conductin. Like APC, APC2 regulates the formation of active betacatenin-Tcf complexes, as demonstrated using transient transcriptional activation assays in APC -/- colon carcinoma cells. Human APC2 maps to chromosome 19p13.3. APC and APC2 may therefore have comparable functions in development and cancer.

Adenomatous Polyposis Coli↗
PubMed1999

Roles of the C terminus of Armadillo in Wingless signaling in Drosophila.

Drosophila melanogaster Armadillo and its vertebrate homolog beta-catenin play multiple roles during development. Both are components of cell-cell adherens junctions and both transduce Wingless (Wg)/Wnt intercellular signals. The current model for Wingless signaling proposes that Armadillo binds the DNA-binding protein dTCF, forming a bipartite transcription factor that activates Wingless-responsive genes. In this model, Armadillo's C-terminal domain is proposed to serve an essential role as a transcriptional activation domain. In Xenopus, however, overexpression of C-terminally truncated beta-catenin activates Wnt signaling, suggesting that the C-terminal domain might not be essential. We reexamined the function of Armadillo's C terminus in Wingless signaling. We found that C-terminally truncated mutant Armadillo has a deficit in Wg-signaling activity, even when corrected for reduced protein levels. However, we also found that Armadillo proteins lacking all or part of the C terminus retain some signaling ability if overexpressed, and that mutants lacking different portions of the C-terminal domain differ in their level of signaling ability. Finally, we found that the C terminus plays a role in Armadillo protein stability in response to Wingless signal and that the C-terminal domain can physically interact with the Arm repeat region. These data suggest that the C-terminal domain plays a complex role in Wingless signaling and that Armadillo recruits the transcriptional machinery via multiple contact sites, which act in an additive fashion.

Amino Acid Sequence↗
PubMed1999

Comparison of the immunogenicity and safety of two 17D yellow fever vaccines.

As part of the clinical validation process of a new working seed of a licensed yellow fever vaccine (new working seed PV26, Stamaril; Pasteur Mérieux Connaught, Lyon, France), the immunogenicity and safety of two batches of this vaccine (PM-YF) were compared with those of another commercially available vaccine (Arilvax; Evans Medical-Wellcome, Liverpool, United Kingdom) in 211 healthy adults. While the geometric mean titer values at days 10-14 and day 28 after vaccination were higher in the PM-YF group, the vaccines provided equivalent seroprotection (titers > or = 1/10) one month after a single vaccine dose (100% PM-YF versus 99% W-YF; P = 0.001, by one-sided equivalence test). Both vaccines were safe. There were no serious local or systemic reactions reported, nor any clinically significant hepatic function abnormalities associated with the use of either vaccine. These two 17D yellow fever vaccines from different European vaccine manufacturers were highly immunogenic and safe, and provided equivalent seroprotection.

Adolescent↗
PubMed1998

Subclavian venogram as a guide to lead implantation.

Recent reports have raised doubts regarding the safety and efficacy of the blind subclavian venipuncture technique for intracardiac lead implantation. To permit a more lateral entry, we used a simple subclavian venogram performed through the brachial vein of the ipsilateral arm of 22 consecutive unselected patients undergoing lead implantation (19 permanent pacemakers and 3 intracardiac defibrillators). A total of 35 leads were implanted (31 left pectoral and 4 right pectoral). Lead insertion by venogram technique was used successfully in all patients. Two inconsequential arterial punctures occurred. There were no pneumothoraces infections, or other complications. Lateral placement should facilitate lead manipulation and minimize "subclavian crush." The method of ipsilateral venogram guided lead insertion appears to be safe and reliable and deserves consideration in patients who require permanent lead placement via the subclavian vein approach.

Adult↗
PubMed1997

Selective feticide by embolization in twin-twin transfusion syndrome. A report of two cases.

BACKGROUND: The early development of complications in twin-twin transfusion syndrome is a poor prognostic sign. For this reason, new techniques for intrauterine therapy are being developed: invasive options, such as selective feticide of one of the twins, have been reported. CASES: Two cases of twin-twin transfusion syndrome in the late second trimester were treated by selective feticide using vascular embolization to the more severely damaged fetus. In one case the embolized fetus was a hydropic recipient with a normal cotwin; in the other, the donor fetus was affected by bilateral hydrocephalus. These fetuses underwent ultrasound-guided embolization using a bolus of histoacryl injected into the umbilical vein and fetal heart. Both patients went on to deliver healthy singletons in the third trimester. CONCLUSION: In twin-twin transfusion syndrome of early onset, embolization may help one of the twins survive. This technique is neither time-consuming nor expensive and does not require a general anesthetic.

Adult↗
PubMed1996

Drosophila alpha-catenin and E-cadherin bind to distinct regions of Drosophila Armadillo.

Adherens junctions are multiprotein complexes mediating cell-cell adhesion and communication. They are organized around a transmembrane cadherin, which binds a set of cytoplasmic proteins required for adhesion and to link the complex to the actin cytoskeleton. Three components of Drosophila adherens junctions, analogous to those in vertebrates, have been identified: Armadillo (homolog of beta-catenin), Drosophila E-cadherin (DE-cadherin), and alpha-catenin. We carried out the first analysis of the interactions between these proteins using in vitro binding assays, the yeast two-hybrid system, and in vivo assays. We identified a 76-amino acid region of Armadillo that is necessary and sufficient for binding alpha-catenin and found that the N-terminal 258 amino acids of alpha-catenin interact with Armadillo. A large region of Armadillo, spanning six central Armadillo repeats, is required for DE-cadherin binding, whereas only 41 amino acids of the DE-cadherin cytoplasmic tail are sufficient for Armadillo binding. Our data complement and extend results obtained in studies of vertebrate adherens junctions, providing a foundation for understanding how junctional proteins assemble and a basis for interpreting existing mutations and creating new ones.

Amino Acid Sequence↗