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Biomedical subjects

S Davis

Publications and source records attributed to S Davis.

At least 37 records · Page 2Linked to original sources

Effectiveness of health education to increase screening for cervical cancer among eastern-band Cherokee Indian women in North Carolina.

BACKGROUND: The North Carolina Native American Cervical Cancer Prevention Project was a 5-year, National Cancer Institute-funded trial of health education designed to increase screening for cervical cancer among Native-American women in North Carolina. PURPOSE: This study was conducted to evaluate the effectiveness of this education program in the Eastern-Band Cherokee target population. METHODS: Cherokee tribal lands were mapped and all households (N = 2223) were listed to ensure maximum coverage of the eligible population (women, aged 18 years and older, who were enrolled tribal members). Eligible women were identified by the use of a brief questionnaire administered to an adult member of the household. Of the 1279 households with eligible women, 1020 (79.8%) agreed to participate. The intervention was an individualized health education program delivered by female Cherokee lay health educators. The participants were randomly assigned to receive or not to receive the intervention (i.e., to program and control groups, respectively) by use of the Solomon Four-Group design. Data were collected in face-to-face interviews conducted in the participant's home. Of the 996 women who were ultimately enrolled, 540 were randomly assigned to receive a pretest (preintervention) interview that involved administration of a 96-item questionnaire designed to collect data on knowledge, intentions, and behaviors related to cervical cancer; of these 540 women, 263 were randomly assigned to receive the education program. The remaining 456 women did not receive the pretest, but 218 were randomly assigned to receive the education program. Six months after receiving the education program, the women in all four groups were administered a post-test that was identical to the pretest. Logistic regression was used to assess the effects of the pretest and the educational program. All P values resulted from two-sided statistical tests. RESULTS: Eight hundred and fifteen (81.8%) of the 996 participants completed the post-test interview. The remaining 181 women who were lost to follow-up were evenly distributed among the four study groups. At the post-test, 282 (73.2%) of the 385 women who received the education program reported having had a Pap smear following the intervention, compared with 275 (64%) of the 430 control subjects. Women who received the education program were more likely to answer all knowledge items correctly on the post-test (odds ratio [OR] = 2.18, 95% confidence interval [CI] = 1.08-4.39) and to report having obtained a Pap smear in the past year (OR = 2.06, 95% CI = 1.14-3.72) than women in the control groups. CONCLUSION: Women who received the education program exhibited a greater knowledge about cervical cancer prevention and were more likely to have reported having had a Pap smear within the past year than women who did not receive the program.

Adult

Elk-L3, a novel transmembrane ligand for the Eph family of receptor tyrosine kinases, expressed in embryonic floor plate, roof plate and hindbrain segments.

The Eph family of receptor tyrosine kinases has 13 distinct members and seven ligands for these receptors have been described to date. These receptors and their ligands have been implicated in regulating neuronal axon guidance and in patterning of the developing nervous system and may also serve a patterning and compartmentalization role outside of the nervous system as well. The ligands are all membrane-attached, and this attachment appears to be crucial for their normal function; five of the known ligands are linked to the membrane via a glycosyl phosphotidylinositol (GPI) linkage, while two of the ligands are transmembrane proteins. Despite the large number of Eph family receptors and ligands, they can be divided into just two major subclasses based on their binding specificities. All the GPI-anchored ligands bind and activate one subclass of the Eph receptors (that represented by Eck) while the two transmembrane ligands bind and activate the other major subclass of receptors (represented by Elk). Here we report the identification and characterization of the third, and most divergent, member of the transmembrane group of Eph ligands, which we term Elk-L3 (Elk-related receptor ligand number 3). Elk-L3 is notable for its remarkably restricted and prominent expression in the floor plate and roof plate of the developing neural tube and its rhombomere-specific expression in the developing hindbrain. The Elk-L3 gene has been localized to mouse chromosome 11 and human chromosome 17.

Amino Acid Sequence

Trends in cancer incidence among children in the U.S.

BACKGROUND: This report provides results of an analysis of temporal trends in childhood cancer incidence in the U.S. stratfied by age, sex, and to a lessor extent, race, within common histologic subtypes. METHODS: Population-based data from nine registries of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute were analyzed. The analysis was limited to children age < or = 14 years. Cancer cases were restricted to those patients with a malignant neoplasm diagnosed between 1974 and 1991; more than 12,000 children were included. Average annual percentage change in incidence rates and corresponding 95% confidence intervals were estimated from the maximum likelihood method of Poisson regression. RESULTS: Among children age < or = 14 years there was a 1% average yearly increase (95% CI 0.6, 1.3) in the incidence rates of all malignant neoplasms combined. The average annual percentage change was similar for males and females, and slightly higher for black children compared with white children. Rates increased an average of 2% or more per year for astroglial tumors, rhabdomyosarcomas, germ cell tumors, and osteosarcomas. The average annual percentage change for acute lymphoid leukemia was 1.6% and trends were somewhat stronger for blacks than whites. Cancer trends, in general, were strongest in young children. In particular, increases in astroglial tumors and rhabdomyosarcomas were most apparent among children age < 3 years, and for retinoblastoma and neuroblastoma among children in their first year of life. The average annual percentage change for acute lymphoid leukemia did not vary dramatically with age, however children age < 2 years had stronger trends compared with older children. We found little evidence for increasing trends in Wilms' tumor, primitive neuroectodermal tumors, or hematopoietic neoplasms other than acute lymphoid leukemia. CONCLUSIONS: These results suggest that cancer occurrence among children within specific histologies increased modestly in the U.S. between 1974 and 1991, and that the increases were most apparent among young children.

Adolescent

Alcoholism: independent predictor of survival in patients with head and neck cancer.

BACKGROUND: Despite recognition of the high prevalence of alcoholism among patients with head and neck cancer, the prognostic importance of alcoholism has not been evaluated adequately. Previous investigators have speculated that alcoholic patients may have a poorer prognosis than nonalcoholic patients because of more advanced stage of cancer, the immunosuppressive effects of alcohol, and an increased rate of death due to other alcohol-related diseases. PURPOSE: The goal of this population-based study was to identify the features of alcoholism that are associated with survival for patients with head and neck cancer and to develop an alcoholic severity staging system from a composite of the independent features of alcoholism. METHODS: This prospective study included 649 patients who were diagnosed with cancer of the oral cavity, oropharynx, hypopharynx, or larynx during the period from September 1, 1983, through February 28, 1987, in a three-county area of western Washington state that participates in the Surveillance, Epidemiology, and End Results Program of the U.S. National Cancer Institute. Details on lifetime alcohol consumption, treatment for alcoholism, abstinence from alcohol prior to the diagnosis of cancer, and alcohol-related health problems were ascertained through in-person interviews near the time of diagnosis. Patients were classified as either nonalcoholics or alcoholics according to their responses to questions from the Michigan Alcoholism Screening Test. The measures of alcohol consumption and abuse that were found to be independently associated with 5-year survival by logistic regression analysis were combined using conjunctive consolidation to create a final composite variable, called an alcoholic severity stage. Cox proportional hazards regression analysis was done to estimate the relative risk (R) of death within 5 years due to specific causes of death for each of the alcoholic severity stages. RESULTS: Alcoholism (RR = 2.06; 95% confidence interval [CI] = 1.43-2.98) and a history of alcohol-related systemic health problems (i.e., liver disease, pancreatitis, delirium tremens, or seizures) (RR = 2.76; 95% CI = 1.69-4.49) were associated with an increased risk of death, whereas abstinence (i.e., the consumption of fewer than one drink per week at 1 year prior to the diagnosis of cancer) (RR = 0.62; 95% CI = 0.39-0.97) was associated with a decreased risk of death. These associations were independent of age, site of cancer, anatomical stage, histopathologic grade, smoking, and type of antineoplastic treatment. Patients in the two worst alcoholic severity stages had an increased risk of dying not only of head and neck cancer but also of cardiovascular disease, pulmonary disease, and other alcohol-related causes. CONCLUSIONS: Alcohol abuse, measured by alcohol consumption, functional impairment, a history of alcohol-related health problems, or abstinence, can provide important prognostic information for patients with head and neck cancer. Our results suggest that sobriety among alcoholic patients can lead to prolonged survival.

Adult

Childhood brain tumor occurrence in relation to residential power line configurations, electric heating sources, and electric appliance use.

To assess the relation between childhood brain tumor occurrence and exposure to potential sources of residential magnetic fields, a population-based case-control study of incident brain tumors was conducted in the Seattle, Washington, area at the Fred Hutchinson Cancer Research Center from 1989 to 1994 among children younger than age 20 years who were diagnosed from 1984 to 1990. The specific aims were to evaluate whether proximity to high-current residential power lines, as defined by the Wertheimer-Leeper code, or use of electric appliances or electric heating sources by the mother while pregnant or by the child before diagnosis were associated with increased risks of brain tumor occurrence. The mothers of 133 cases and 270 controls (recruited by random digit dialing) participated. Risk of brain tumor occurrence did not increase with increasing exposure, as indicated by the five-level Wertheimer-Leeper code. When exposure was dichotomized as high versus low, the odds ratio was 0.9 (95% confidence interval 0.5-1.5) and did not vary significantly by sex, age, or histology. No elevations in risk were found for ever versus never use of electric blankets, water beds, or electric heating sources. Odds ratios were slightly elevated for nine appliances and were at or below 1.0 for eight others. These data do not support the hypothesis that exposure to magnetic fields from high-current power lines, electric heating sources, or electric appliances is associated with the subsequent occurrence of brain tumors in children.

Adolescent

In vitro activation of the interferon-induced, double-stranded RNA-dependent protein kinase PKR by RNA from the 3' untranslated regions of human alpha-tropomyosin.

The cellular kinase known as PKR (protein kinase RNA-activated) is induced by interferon and activated by RNA. PKR is known to have antiviral properties due to its role in translational control. Active PKR phosphorylates eukaryotic initiation factor 2 alpha and leads to inhibition of translation, including viral translation. PKR is also known to function as a tumor suppressor, presumably by limiting the rate of tumor-cell translation and growth. Recent research has shown that RNA from the 3' untranslated region (3'UTR) of human alpha-tropomyosin has tumor-suppressor properties in vivo [Rastinejad, F., Conboy, M. J., Rando, T. A. & Blau, H. M. (1993) Cell 75, 1107-1117]. Here we report that purified RNA from the 3'UTR of human alpha-tropomyosin can inhibit in vitro translation in a manner consistent with activation of PKR. Inhibition of translation by tropomyosin 3'UTR RNA was observed in a rabbit reticulocyte lysate system, which is known to contain endogenous PKR but was not seen in wheat germ lysate, which is not responsive to a known activator of PKR. A control RNA purified in the same manner as the 3'UTR RNA did not inhibit translation in either system. The inhibition of translation observed in reticulocyte lysates was prevented by the addition of adenovirus virus-associated RNA1 (VA RNAI), an inhibitor of PKR activation. Tropomyosin 3'UTR RNA was bound by immunoprecipitated PKR and activated the enzyme in an in vitro kinase assay. These data suggest that activation of PKR could be the mechanism by which tropomyosin 3'UTR RNA exerts its tumor-suppression activity in vivo.

Animals

The cosmobiological balance of the emotional and spiritual worlds: phenomenological structuralism in traditional Chinese medical thought.

This paper points to a convergence of formal and rhetorical features in ancient Chinese cosmobiological theory, within which is developed a view of the inner life of human emotions. Inasmuch as there is an extensive classical tradition considering the emotions in conjunction with music, one can justify a structural analysis of medical texts treating disorder in emotional life, since emotions, musical interpretation and structural analysis all deal with systems interrelated in a transformational space largely independent of objective reference and propositional coordination. Following a section of ethnolinguistic sketches to provide grounds in some phenomenological worlds recognized by Chinese people, there is a textual analysis of a classical medical source for the treatment of emotional distress. Through close examination of the compositional schema of this text, it can be demonstrated that the standard categories of correlative cosmology are arrayed within a more comprehensive structural order.

Emotions

Small, low-cost implantable centrifugal pump for short-term circulatory assistance.

BACKGROUND: In 1991, Allegheny General Hospital and Allegheny-Singer Research Institute purchased a centrifugal pump, then a 2-year-old technology, from Medtronic Bio-Medicus, as part of its research program for novel treatments of acute and chronic heart failure. During a 4-year development program, we then established and met goals of durability, performance, thromboresistance, and low cost. METHODS: In vitro testing involved extensive hydraulic characterizations using Penn State mock loops. Calorimetry was used to determine efficiency. Durability studies used heated (37 degrees C) seawater for 28 to 45 days. In vivo studies used 46 sheep to test performance and engineering changes and to determine myocardial oxygen consumption, thromboresistance, and long-term durability. A left atrium-to-aorta circuit was used in all. RESULTS: Hydraulic testing showed no preload sensitivity but moderate afterload sensitivity at all impeller speeds (2,000 to 6,000 rpm). The heat load was low, and overall efficiency was 13% to 15%. Bench durability studies showed no electrical malfunction of the stator or console without degradation of the biomaterials used. Acute in vitro studies showed a near-linear relationship of myocardial oxygen consumption and left ventricular stroke work, pump flow, and pump speed. At speeds of 2 to 3 L/min (50% bypass), left ventricular stroke work and myocardial oxygen consumption were decreased approximately 50%. Additionally, 5 animals have had implants for 28 to 154 days with no macroemboli or microemboli detected in any animal. Hematologic and biochemical studies became normal 3 to 7 days after implantation. Hemolysis was low at less than 10 mg/dL. Clinical costs of the device are estimated to be 80% less than those of currently available devices. CONCLUSIONS: We conclude that an old technology has been made into new technology by application of sound engineering design principles, microchips, and new biomaterials. Qualifying trails for a Food and Drug Agency investigational device exemption application are in progress.

Animals

Activation of metabotropic glutamate receptors induce differential effects on synaptic transmission in the dentate gyrus and CA1 of the hippocampus in the anaesthetized rat.

Activation of ACPD-sensitive metabotropic receptors induced differential effects on synaptic transmission and the induction of LTP in CA1 and the dentate gyrus of the hippocampus i.c.v. injections of (1.S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD] induced enduring potentiation of the fEPSP in CA1, which occluded tetanically induced LTP. In contrast, ACPD induced a dose-dependent biphasic effect on the fEPSP in the dentate gyrus, consisting of an initial short lasting potentiation, followed by enduring depression of the response, and blockade of LTP. These two effects are likely to be mediated by two different classes of the receptor as in the dentate gyrus the selective class I agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG) induced sustained potentiation of the fEPSP, whereas the mixed mGluR2 agonist-mGluR1 antagonist, (S)-4-carboxy-3-hydrophenylglycine((S)-4C3H-PG) induced only depression. Increasing the concentration of calcium directly in the dentate gyrus prior to, and in conjunction with, injections of ACPD induced sustained potentiation rather than depression. The differential effects indicate that the second messenger cascades the subtypes of receptors are linked with, mediate different forms of synaptic plasticity within the hippocampus and have important implications for their role in learning.

Animals

Radiotherapy for early infradiaphragmatic Hodgkin's disease: the Australasian experience.

PURPOSE: To review the Australasian results of Stage I and IIA Infradiaphragmatic Hodgkin's Disease (IHD) treated solely by irradiation. METHODS AND MATERIALS: Eligible patients had IHD only and were treated by irradiation with curative intent over the period of 1969 to 1988. Ten radiation oncology centres from within Australia and New Zealand were surveyed for patient, tumour and treatment variables. Disease free rates, survival and complications were analysed. RESULTS: 106 patients with IHD were studied. The average potential follow up was 9.4 years. The male to female ratio was 3.3:1. The median age was 37.5 years. Histological subgroups were as follows; lymphocyte predominant 43%, mixed cellularity 21%, lymphocyte depleted 5%, nodular sclerosing 27% and unclassifiable 4%. Fifty nine patients had laparotomy of which 22 (37%) were positive for tumour. Nine laparotomies were performed for diagnosis and the remainder for staging. One patient was up-staged by laparotomy and three were down-staged. Sixty-eight patients presented with inguinal disease alone, five with abdominal disease alone, 19 with two sites of involvement and 12 with inguinal, pelvic and abdominal disease. In two patients the site was unknown. There was no correlation between site of involvement, age, sex or histological subtype. Forty seven cases were clinically staged (CS) as follows: CS IA-23, CS IIA-24. The other 59 were pathologically staged (PS) as follows: PS IA-37, PS IB-1, PS IIA-21. Treatment consisted of involved field alone (16), inverted Y (68), inverted Y and spleen (13), para-aortic irradiation only (3), or total nodal irradiation (6). Mean dose was 37 Gy. There were 30 recurrences to give an acturial 10-year disease-free rate of 70%. In multivariate analysis lower number of tumour sites, lymphocyte predominant histology and higher dose were all significantly correlated with higher disease free rates. Eight patients died of Hodgkin's disease and 19 of other causes. The 10-year overall survival rate was 71%. Older age and higher number of disease sites were significantly correlated with shorter survival. Fourteen of 30 relapses may have been avoidable by the use of total nodal irradiation. In particular ten of 21 patients with abdominal disease relapsed in nodal sites which would have been covered by total nodal irradiation. CONCLUSIONS: The rate of control in IHD could perhaps be improved by avoiding involved field irradiation or by aggressive therapy with total nodal irradiation or combined modality chemo-irradiation in Stage II disease. Staging laparotomy does not appear to be indicated.

Abdominal Neoplasms

Homozygosity mapping of Hallervorden-Spatz syndrome to chromosome 20p12.3-p13.

Hallervorden-Spatz syndrome (HSS) (OMIM #234200) is a rare, autosomal recessive neurode-generative disorder with brain iron accumulation as a prominent finding. Clinical features include extrapyramidal dysfunction, onset in childhood, and a relentlessly progressive course. Histologic study reveals massive iron deposits in the basal ganglia. Systemic and cerebrospinal fluid iron levels are normal, as are plasma levels of ferritin, transferrin and ceruloplasmin. Conversely, in disorders of systemic iron overload, such as haemochromatosis, brain iron is not increased, which suggests that fundamental differences exist between brain and systemic iron metabolism and transport. In normal brain, non-haem iron accumulates regionally and is highest in basal ganglia. Pathologic brain iron accumulation is seen in common disorders, including Parkinson's disease, Alzheimer's disease and Huntington disease. In order to gain insight into normal and abnormal brain iron transport, metabolism and function, our approach was to map the gene for HSS. A primary genome scan was performed using samples from a large, consanguineous family (HS1) (see Fig. 1). While this family was immensely powerful for mapping, the region demonstrating homozygosity in all affected members spans only 4 cM, requiring very close markers in order to detect linkage. The HSS gene maps to an interval flanked by D20S906 and D20S116 on chromosome 20p12.3-p13. Linkage was confirmed in nine additional families of diverse ethnic backgrounds.

Chromosome Mapping

Effect of space flight on cytokine production and other immunologic parameters of rhesus monkeys.

During a recent flight of a Russian satellite (Cosmos #2229), initial experiments examining the effects of space flight on immunologic responses of rhesus monkeys were performed to gain insight into the effect of space flight on resistance to infection. Experiments were performed on tissue samples taken from the monkeys before and immediately after flight. Additional samples were obtained approximately 1 month after flight for a postflight restraint study. Two types of experiments were carried out throughout this study. The first experiment determined the ability of leukocytes to produce interleukin-1 and to express interleukin-2 receptors. The second experiment examined the responsiveness of rhesus bone marrow cells to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Human reagents that cross-reacted with monkey tissue were utilized for the bulk of the studies. Results from both studies indicated that there were changes in immunologic function attributable to space flight. Interleukin-1 production and the expression of interleukin-2 receptors was decreased after space flight. Bone marrow cells from flight monkeys showed a significant decrease in their response to GM-CSF compared with the response of bone marrow cells from nonflight control monkeys. These results suggest that the rhesus monkey may be a useful surrogate for humans in future studies that examine the effect of space flight on immune response, particularly when conditions do not readily permit human study.

Animals

Acquisition of services recommended by a multidisciplinary medical diagnostic team for children under three years of age evaluated for developmental delays.

After multidisciplinary medical diagnostic teams evaluate children with developmental delays, they recommend to parents that they seek specific services, but the team rarely knows which services are obtained. We sought to determine which services pursued by the parents were actually acquired and to determine if there were barriers to the acquisition of services. In a diagnostic clinic located in a teaching hospital in an urban setting, we evaluated 92 children less than 3 years of age mainly from an inner city population. At a family conference, the parents had indicated an interest in pursuing an average of 1.87 +/- 1.34 social services, 1.70 +/- 1.32 educational services, and 3.61 +/- 2.31 medical services recommended by the team. Four months after the family conference, the actual services obtained by families included 38.5% of the social services, 70.87% of the educational services, and 71.36% of the medical services. Significantly fewer social services were obtained than educational and medical services.

Chicago

Brain structure and task-specific increase in expression of the gene encoding syntaxin 1B during learning in the rat: a potential molecular marker for learning-induced synaptic plasticity in neural networks.

The mRNAs encoding the synaptic vesicle proteins syntaxin 1B and synapsin I were measured using in situ hybridization in several brain regions--the dentate gyrus, CA3 and CA1 of the hippocampus, the parietal, the motor and prefrontal cortices and the core and shell of the accumbens--of rats that were learning a spatial reference or working memory task on a radial arm maze. The mRNA encoding syntaxin 1B was significantly increased in all hippocampal regions in rats learning the working memory task, whereas it was increased in the prelimbic area of the prefrontal cortex and the shell of the accumbens in rats learning the spatial reference memory task. No change in mRNA encoding syntaxin 1B was observed in the motor and parietal and cortices or the core of the accumbens, and the mRNA encoding synapsin I was not significantly different from that of naive caged controls or rats running the maze for continuous reinforcement in any of the brain structures examined. These results demonstrate that the gene encoding a key member of synaptic vesicle function is up-regulated in a task- and brain-specific manner during learning. They are discussed in terms of the potential role this protein may play in trans-synaptic propagation of plasticity within specific neural networks as a function of the information required in the laying down of different types of memory.

Animals

Validation of the doubly labelled water technique for bumblebees Bombus terrestris (L.)

The doubly labelled water (DLW) technique was validated for the bumblebee Bombus terrestris (L.) using respirometry (RESP) from tethered roundabout flights. We injected small volumes (1 &micro;l) of a mixture containing low concentrations of deuterium and 18O and withdrew 1-2 &micro;l of haemolymph to determine initial 18O concentration. The injected isotopes were equilibrated with the body water pool after 10 min, and high material turnover allowed the analysis of final blood isotope concentrations after 5-7 h. On average (n=16), values measured using the DLW technique exceeded values measured using RESP by 3.1&plusmn;9.9 %, a difference that was not statistically significant at the 99 % confidence level. The absolute error was 7.4&plusmn;7.1 % (mean &plusmn; s.d.). Isotope dilution spaces of both deuterium and 18O were almost identical with the body water pool. We corrected for isotope fractionation, using a slightly higher value than usual for one of the fractionation factors. The single most important variable to influence DLW results, which could not be measured with the desired accuracy, was the volume of the final body water pool N. An overestimate of final N possibly resulted in the DLW overestimate.

Journal Article

The melatonin hypothesis: electric power and breast cancer.

Breast cancer is a disease of modern life. As societies industrialize, risk increases, yet it is unclear which of the myriad changes coming with industrialization drives this increase. One important hallmark of modern life is the pervasive use of electric power. Electric power produces light at night (LAN) and electric and magnetic fields (EMF), either or both of which may alter pineal function and its primary hormone melatonin, thereby, perhaps increasing the risk of breast cancer. This hypothesis, stated a decade ago, is now receiving considerable experimental and epidemiological attention. The circumstantial case for the hypothesis has three aspects: light effects on melatonin, EMF effects on melatonin, and melatonin effects on breast cancer. The strongest of these aspects is the effects of light on melatonin. It is clear that the normal nocturnal melatonin rise in humans can be suppressed by light of sufficient intensity. The evidence for an effect of melatonin on breast cancer in experimental animals is strong, but the evidence in humans is scant and difficult to gather. The weakest aspect of the circumstantial case is EMF effects on melatonin. Whereas a half dozen independent laboratories have published findings of suppression in animals, there are inconsistencies, and there are no published data on humans. The direct evidence bearing on the hypothesis is sparse but provocative. Two laboratories have published data showing substantial increases in chemically induced breast cancer in rats by a weak AC (alternating current) magnetic field. The epidemiological evidence is very limited but has offered some support as well. An effect of electric power on breast cancer would have profound implications, and this possibility deserves continued investigation.

Animals