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Biomedical subjects

C Kirkpatrick

Publications and source records attributed to C Kirkpatrick.

At least 37 records · Page 2Linked to original sources

Armadillo is required for adherens junction assembly, cell polarity, and morphogenesis during Drosophila embryogenesis.

Morphological and biochemical analyses have identified a set of proteins which together form a structure known as the adherens junction. Elegant experiments in tissue culture support the idea that adherens junctions play a key role in cell-cell adhesion and in organizing cells into epithelia. During normal embryonic development, cells quickly organize epithelia; these epithelial cells participate in many of the key morphogenetic movements of gastrulation. This prompted the hypothesis that adherens junctions ought to be critical for normal embryonic development. Drosophila Armadillo, the homologue of vertebrate beta-catenin, is a core component of the adherens junction protein complex and has been hypothesized to be essential for adherens junction function in vivo. We have used an intermediate mutant allele of armadillo, armadilloXP33, to test these hypotheses in Drosophila embryos. Adherens junctions cannot assemble in the absence of Armadillo, leading to dramatic defects in cell-cell adhesion. The epithelial cells of the embryo lose adhesion to each other, round up, and apparently become mesenchymal. Mutant cells also lose their normal cell polarity. These disruptions in the integrity of epithelia block the appropriate morphogenetic movements of gastrulation. These results provide the first demonstration of the effect of loss of adherens junctions on Drosophila embryonic development.

Actin Cytoskeleton↗

Therapy of bacterial vaginosis using exogenously-applied Lactobacilli acidophili and a low dose of estriol: a placebo-controlled multicentric clinical trial.

The efficacy of vaginal tablets (Gynoflor) containing 50 mg of a lyophilisate of viable, H2O2-producing Lactobacillus acidophilus (at least 10(7) colony forming units/tablet) and 0.03 mg estriol (CAS 50-27-1) for the treatment of bacterial vaginosis (BV) was tested in a multicentric, randomised, placebo-controlled clinical trial with parallel-group design. 32 non-menopausal women with positive diagnoses for BV, including intermediate cases, participated in the trial. Patients were diagnosed using the classical clinical parameters of BV according to Amsel and using microscopic analysis of the Gram-stained vaginal smear. A positive clinical diagnosis of BV required at least 2 of the following 4 clinical criteria to be positive; greyish-white, homogeneous leukorrhea; vaginal pH > 4.5; KOH test for volatile amines; presence of clue cells. Microscopic diagnosis of BV, on the other hand, was obtained if examination of the Gram-stained vaginal smear showed less than 6 lactobacilli per field of view (1000 x magnification). This corresponds to another definition of BV as "lactobacilli deficiency syndrome". The efficacy of the 6-day therapy with 1-2 vaginal tablets daily was evaluated using both clinical and microscopic analysis. Using Amsel's classical clinical parameters of BV, the cure rate (defined as < or = 1 of the 4 clinical criteria positive) two weeks after the start of therapy was 77% in the verum group and 25% in the placebo group. Four weeks after the start of therapy, the cure rate was 88% in the verum group and 22% in the placebo group. At both control examinations, the cure rate for the test group was significantly higher than that for the placebo group (p < 0.05, Fisher's exact test, 2-sided, significance level 0.05). In addition, the trial showed that after 6 days of treatment with the test preparation, the lactobacilli were capable of recolonising the vagina. A significant increase in the number of lactobacilli was observed in the Gram-stained vaginal smear for the patient group treated with the test preparation compared to the placebo patient group (p < 0.05, Fisher's exact test, 2-sided, significance level 0.05), two and four weeks after the start of the 6-day treatment.

Adult↗

Management of the growth-restricted fetus: the role of noninvasive tests and fetal blood sampling.

OBJECTIVE: To assess the accuracy of two noninvasive tests, the nonstress test (NST) and Doppler velocimetry of the umbilical artery, in predicting fetal acidemia or hypoxia demonstrated by funipuncture, and to determine any association between acidemia or hypoxia and perinatal outcome. METHODS: The study included 112 consecutive growth-restricted fetuses diagnosed by ultrasonography between 26-39 weeks' gestation. For Doppler sonograms, the absence of end-diastolic flow was considered pathologic. Acidemia and hypoxia were defined as a pH and an oxygen pressure (PO2) below the fifth percentile at the given gestational age. The fetuses were classified according to the results obtained by the different tests (Doppler velocimetry, NST, cord blood gases). RESULTS: Fetuses with one or both noninvasive tests abnormal (group A, N = 32) had a significantly lower mean gestational age at sampling than those fetuses with both noninvasive tests normal (group B, N = 80). Mean pH and PO2 values for groups A and B were significantly different. Obstetric and perinatal data were collected, and a statistically significant difference was demonstrated between those with a pH and/or PO2 below the fifth percentile and those with a pH and PO2 above the fifth percentile for all indices except birth weight below the tenth percentile. CONCLUSION: Fetal growth restriction is a benign condition in physically normal fetuses if both noninvasive tests and pH and PO2 measured by funipuncture are normal in the absence of maternal pathology. One single fetal blood analysis for pH and PO2 helped separate groups having different obstetric and neonatal outcomes.

Female↗

Not just glue: cell-cell junctions as cellular signaling centers.

Proper cell-cell adhesion and communication are essential for normal development and are often perturbed during tumor formation. We have come to realize that cell-cell junctions not only mediate intercellular adhesion, but also serve as organizing centers for specific cell-cell signaling pathways. The characterization of protein components of adhesive and tight/septate junctions in vertebrates and Drosophila is reviewed, and their roles in adhesion and signaling discussed. Many molecules that mediate intercellular signaling, including certain tumor suppressor gene products, are localized to particular cell-cell junctions, suggesting that disruption of junctional signaling pathways contributes to tumorigenesis.

Animals↗

Focus on autonomy: supporting an innovative, empowered staff.

Current nursing literature documents the benefits of nurse autonomy with evidence of increased job satisfaction. Health care organizations can support autonomous behavior through empowerment. This article reports how one hospital is responding to nurses' requests for empowerment. The request to focus the nursing division's efforts to enable an innovative empowered staff was initiated during an annual planning session with clinical and administrative staff participation. The first phase of the project involved baseline measurements of autonomy and strategic planning for empowerment through education and leadership modeling. Initial autonomy studies were conducted in 1994 and will be repeated at 18, 36, and 48 months.

Humans↗

Technical note: digital radiographic pelvimetry--a novel, low dose, accurate technique.

A technique is described for lateral pelvimetry which results in a lower radiation dose than that resulting from conventional film-screen pelvimetry and computed tomography (CT) pelvimetry. It uses digital radiographic imaging thereby closely matching conventional techniques yet additionally providing post-processing facilities including distance measurement and contrast adjustment. The digital technique was evaluated with an anthropomorphic phantom and compared with the conventional technique by measuring entrance surface doses on two groups of post-natal patients. Digital radiography gave radiation doses 10 times lower than those using conventional techniques.

Female↗

Postpartum ovarian veins thrombophlebitis.

Puerperal ovarian vein thrombophlebitis (POVT) is a rare postpartal complication. Its incidence is about 0.05%. POVT can follow a term pregnancy, a premature delivery, an abortion or an ectopic pregnancy. POVT usually presents as a syndrome consisting in lower abdominal pain and fever which does not respond to adequate antibiotics. We present a case report, in which the diagnosis was based upon computed tomography.

Adult↗

Bovine and human endothelial cell growth on collagen microspheres and their infection with the rickettsia Cowdria ruminantium: prospects for cells and vaccine production.

We successfully cultivated the rickettsia Cowdria ruminantium, in bovine endothelial cell lines (Bovine Umbilical Endothelial Cells/BUEC and Bovine microvasculature Cells/BMC) and also in primary endothelial cells of bovine origin (Bovine Aorta Endothelial cells/BAEC) and more surprisingly in cells of human origin--Human Umbilical Vein Endothelial Cells/HUVEC--and Human Endothelial Cells from the Microvasculature/HEMEC. This first evidence of the pathogenicity of this bovine rickettsia in the human cell system gene-rates new interest as regards its possible relevance for human health. It provides also further possibilities for the attenuation of Cowdria ruminantium isolates, and therefore brings new prospects for vaccine preparation. In vaccine production, mass cell culture is essential. Our results indicate that endothelial cells attach efficiently on collagen microspheres. As BAEC cells grow well on them in a batch mode, and if the process could be optimized for the different cell types (using appropriate adhesion and growth factors) our observations offer interesting prospects for the future development of a Cowdria ruminantium vaccine production in the fluidized-bed reactor VERAX System one, which provides easy control of growth conditions.

Animals↗

Assessing utility of single photon emission computed tomography (SPECT) scan in Alzheimer disease: correlation with cognitive severity.

Diagnosis of probable Alzheimer disease (AD) is made by a combination of characteristic clinical findings, when normal laboratory studies reveal no structural or metabolic cause of the dementia. Definite diagnosis of AD, however, can only be made with brain tissue examination. PET scanning reveals parietotemporal decreases in cerebral blood flow (CBF) and glucose metabolism that differentiate AD from normal elderly and from multi-infarct dementia. Preliminary studies suggest that similar defects in CBF are detectable in single photon emission computed tomography (SPECT) in AD. Utilizing the iodinated ligand [123I] HIPDM ([123I] hydroxyiodobenzylpropanediamine), we studied 19 patients with probable AD of varying severity, with emphasis on mild cases, to assess the utility of SPECT as a diagnostic test in AD. Parietotemporal perfusion on SPECT was decreased unilaterally or bilaterally in 16 of 19 AD patients, similar to the defects reported with PET. The degree and extent of decreased CBF on SPECT correlated with AD severity. Strong correlations were obtained between decreases in computer-generated ratios of parietal to cerebellar activity and the level of cognitive function. SPECT was read as normal (on the radiographic film) by the nuclear medicine physician in all cases with Mini-Mental State (MMS) score greater than 24, and showed bilateral parietal perfusion deficits in only 1 of 4 patients with MMS between 22 and 24. Ten of 12 patients with MMS less than or equal to 21 had bilateral parietal abnormalities; the other 2 had unilateral perfusion defects. All patients with MMS less than 15 were bilaterally abnormal. SPECT is less expensive and more widely available than PET, and may have an adjunctive role in diagnosis of AD and other dementias if utilized under the proper circumstances.

Aged↗

Prenatal screening for gestational diabetes throughout office hours.

A group of 1666 consecutive pregnant women attending our prenatal clinic was screened for gestational diabetes (GD). Patients with risk factors (155) underwent a classical 50 g OGTT, while 1511 patients without risk factors for GD were submitted at random throughout the day to a simplified OGTT, consisting of a single blood glucose determination 1 h after the glucose ingestion. In these patients, plasma glucose 1 h after the glucose load averaged 104 +/- 1 mg/dl and exceeded 135 mg/dl in 315 patients. In the latter group, retested with a standard 50 g OGTT, 48 out of 1511 patients (3.2%) finally met the criteria for GD, while 25 patients had an abnormal OGTT in the group with risk factors. The blood glucose levels after simplified 50 g glucose load were significantly higher in the third (vs. first) trimester of pregnancy (113 +/- 1 vs. 96 +/- 1 mg/dl, p less than 0.001). A significant increase in mean glucose concentrations was also observed for those patients tested after 11 a.m. (107 +/- 1 mg/dl vs. 99 +/- 1 mg/dl prior to 11 a.m. p less than 0.001) and for the women with an ideal body weight (IBW) greater than or equal to 150% at the beginning of pregnancy (124 +/- 7 mg/dl vs. 104 +/- 1 mg/dl for less than 150% IBW, p less than 0.001). These variations in glucose tolerance, related to the time of the day, the gestational age and the body weight, are of limited amplitude and should not be considered in the determination of the cut-off point of the screening test. Glucose loading at random throughout the day is a simple and useful tool for the routine detection of unsuspected GD in pregnant patients attending prenatal clinics.

Belgium↗

A social and clinical evaluation of centenarians.

A social and clinical evaluation was performed on thirty Kentucky centenarians. The majority of the subjects were women (19/30), white (27/30), either widows or widowers (26/30), and lived in long term care facilities (15/30). Only one of thirty had ever smoked cigarettes and there was an absence of excessive alcohol use. Medication use varied from 0 to 9 medications. Digitalis, diuretics, and anti-inflammatory medications were common (12; 16; 15 respectively) while major and minor tranquilizers were less frequently used (7 and 4). Hypertension was present in 48%. Although rarely functionally significant, clinically evident cardiac disease was present in 38%. Ninety-three percent lacked vibratory sensation at the ankles while ankle jerks were absent in 82%. Functionally significant diminished vision and hearing were frequent (40% and 60% respectively). Functional assessment demonstrated moderate to nearly complete independence in 57%, while the remaining 43% were significantly to nearly totally dependent on others. The primary conclusion is that for all they have in common, centenarians remain unique individuals with a tremendous variability among themselves.

Aged↗

Fatal ureaplasma infection in second twin born 60 days after delivery of the first in a patient with recurrent spontaneous abortion--a case report.

A delay of more than one month between the birth of twins is an unusual occurrence presenting the obstetrician and the neonatalogist with many questions regarding the management of the case. There is the risk of prematurity for the second twin as labor has already occurred in the pregnancy. There is also a risk of infection to both mother and fetus during the interval between the two deliveries, since the stump of the first twin's cord may precipitate ascending colonization from vagina and cervix. Germs frequently recovered from the vagina e.g. Ureaplasma urealyticum, are associated with prematurity. The latter has also been responsible for lethal interstitial pneumonia in the neonate. We present a case of a patient who though she delivered twice normally, had suffered 4 first trimester abortions and one late abortion, all spontaneous. Her eighth pregnancy was a twin pregnancy. She underwent a cerclage at 14 weeks, but went into labor at 17 weeks, when she delivered the first macerated twin. She was then treated with fenoterol and ampicillin; nevertheless she delivered twin the second at 26 weeks. This 750 g baby-girl presented with severe respiratory distress. Repeated chest X rays showed perihilar infiltrates which became nodular. All cultures were negative. At the end of the first week, when her condition was considered satisfactory, she deteriorated dramatically and died in respiratory failure and DIC. Tracheal aspirates were positive for Ureaplasma urealyticum.

Abortion, Habitual↗

Imaging the centenarian brain. A computed tomographic study.

Ten healthy and mentally alert centenarians underwent cranial computed tomography (CT) using a fourth-generation CT scanner. The subjects ranged in age from 100 to 102 years, and included six women and four men. Two of them used alcohol on a daily basis and five had systolic blood pressures of at least 160 mmHg. The CT scans demonstrated considerable variation in the degree of cerebral atrophy, which had no relation to either sex, alcohol use, or hypertension. Three of the centenarians had evidence of mild periventricular white matter lucency. Although progressive cerebral atrophy is an integral aspect of the normal aging process in the very elderly, its exact relationship to cognitive function remains unclear.

Aged↗

Analysis of proteins synthesized by fibroblasts from patients with cystic fibrosis by two-dimensional gel electrophoresis and double label autoradiography.

Mucoviscidosis, the most frequently lethal genetic syndrome of Caucasian population, is a recessive disease with multiple tissue involvement. Although the major pathological changes are observed in lungs and pancreas, abnormalities have also been detected in several other exocrine glands. For many reasons, such as the ready availability of tissue material, the absence of secondary changes and the potential for prenatal diagnosis, cultured skin fibroblasts could be the tissue of choice to search for the primary defect. Several abnormalities have been reported in CF fibroblasts, suggesting that the genetic abnormality is expressed in these cells. To search for potentially mutant protein(s) we have compared the protein composition of normal and CF fibroblasts by two dimensional gel electrophoresis and double-labeling autoradiography using 35S and 75Se methionine as tracer. The results demonstrate the power of the method; however, we have not found one protein spot consistently missing in CF cells. Possible reasons for the absence of a single common identifiable defect are discussed.

Adolescent↗

The immune status of healthy centenarians.

The immune status of 17 healthy individuals 100-103 years of age (centenarians) was investigated. Qualitative values for immunoglobulins IgG, IgM, IgA, and IgE were within normal ranges for subjects more than 60 years of age with the exception of elevated IgM in one individual. Cell marker studies employing a panel of 27 monoclonal antibodies delineating T and B lymphocytes, monocytes, natural killer cells, granulocytes, and functional and developmental subsets of each were performed to phenotype the peripheral blood leukocytes. Although the total lymphocyte count was normal in every subject, the numbers of T4-positive helper-inducer T lymphocytes were profoundly depressed, as were responses to the mitogen phytohemagglutinin and interleukin-2 production. Activated immature T lymphocytes and the number of cells bearing the phenotype of natural killer cells were increased, but natural killer cell activity was normal. Early B lymphocytes were also increased. The relative concentration of monocytes was normal. Taken together these findings indicate that the immune system in centenarians is similar to that in younger but still elderly individuals, i.e., discriminating T-lymphoid functions are reduced in association with an apparent failure of some T, B, and natural killer cells to differentiate to functional maturity.

Activities of Daily Living↗