The Newcastle exercise project. Key messages are misleading and conclusions are not evidence based.
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Data Interpretation, Statistical↗
Biomedical subjects
C Woods
Publications and source records attributed to C Woods.
Measuring cell proliferation in the rectal mucosa. comparing bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) assays.
Cell proliferation in the human colorectum can be measured using bromodeoxyuridine (BrdU) or proliferating cell nuclear antigen (PCNA) assays. Using data from the National Cancer Institute's Polyp Prevention Trial, these two assays are compared using correlation coefficients and variance components analysis. Adjusting for fixed as well as for the random effects of between-biopsy and scoring variation, the estimated correlation is 0.46 for the log labeling index and 0.45 for log proliferative height. This is an estimate of the highest correlation that can be achieved by taking multiple biopsies scored by multiple scorers. For single biopsies, the estimated correlation is 0.16 and 0.10, respectively. There are significant differences between the variance components for the two assays. For example, for log labeling index, PCNA has a lower variation between biopsies than BrdU, but higher variation between scorings. When used in a clinical or epidemiological setting, it is important to take multiple biopsies at multiple time points.
Adenoma↗
Report of the first human case of lobomycosis in the United States.
We describe the first human case of lobomycosis caused by Lacazia loboi in a 42-year-old white male resident of Georgia. The patient had traveled to Venezuela 7 years earlier, where he had planned to rappel down Angel Falls in Canaima. Although he never actually rappelled the falls, he did walk under the falls at least three times, exposing himself to the high water pressures of the falls. He noticed a small pustule with surrounding erythema developing on the skin of his right chest wall. The lesion gradually increased in size and had an appearance of a keloid. For cosmetic reasons, the patient sought medical treatment to remove the lesion. After an uncomplicated excision of the lesion, the patient recovered completely. The excised tissue was fixed in formalin for pathologic examination. Tissue sections stained by hematoxylin and eosin, periodic acid-Schiff stain, and Gomori methenamine silver stain procedures showed numerous histiocytes, multinucleated giant cells, and numerous globose or subglobose, lemon-shaped cells producing multiple blastoconidia connected by narrow tube-like connectors and catenate chains of various lengths characteristic of L. loboi.
Adult↗
Trends in human immunodeficiency virus (HIV) counseling, testing, and antiretroviral treatment of HIV-infected women and perinatal transmission in North Carolina.
Since 1993, trends in perinatal human immunodeficiency virus (HIV) transmission have been monitored by use of chart review of patients identified at a central diagnostic laboratory. In the population studied, either pre- or postnatal antiretroviral therapy to the infant increased from 21% in 1993 to 95% in 1997. Concurrently, the number of HIV-infected infants declined from 25 in 1993 to 4 in 1997. The complete Pediatric AIDS Clinical Trials Group Protocol 076 regimen was the most effective in reducing transmission (3.1%). Twenty-two of 35 infants who became infected in 1995-1997 had mothers who did not receive antiretroviral therapy, although counseling practices improved with time. In 1995, 87% of the mothers of HIV-seropositive infants were counseled, whereas in 1997, 96% were counseled (P<.005). None of 59 infants tested had high-level phenotypic zidovudine resistance, although 5 (8.8%) of 57 infants had virus isolates with at least one mutation in the reverse transcriptase gene associated with reduced phenotypic susceptibility to zidovudine.
Anti-HIV Agents↗
Induction of antibody response by DNA immunization of newborn baboons against influenza virus.
Previous studies showed that DNA immunization of newborn mice with plasmids expressing influenza virus antigens induced protective immunity. We have now extended the study of neonatal responsiveness to DNA vaccines to nonhuman primates. Baboons immunized as neonates with plasmids expressing type A influenza virus hemagglutinin (HA) and nucleoprotein (NP) in doses ranging from 40 microg to 1 mg per plasmid per dose developed virus-specific humoral responses. The titer and kinetics of appearance of virus-specific IgG antibodies were dose dependent. Specific antibodies were detected by enzyme-linked immunosorbent assay (ELISA) as early as 1 month after birth in baboons immunized with the highest and intermediate doses of vaccine. Virus-neutralizing antibodies were detected in the group of baboons immunized with the highest dose. The specificity of virus-neutralizing antibodies was found to be directed against homologous determinants of HA; however, the IgG antibodies also cross-reacted with HA of a drift variant. Thus, DNA vaccination of newborn baboons with a prototype vaccine against influenza virus resulted in induction of specific humoral immunity.
Animals↗
Clinical performance of an innovative back surface multifocal contact lens in correcting presbyopia.
PURPOSE: This prospective study was designed to subjectively and objectively evaluate the performance of an aspheric multifocal back surface rigid gas permeable (RGP) contact lens. The multifocal element of this lens design consisted of an aspheric optical zone that varied according to the patient's ametropia, corneal topography, and required reading addition. METHODS: We fit 28 presbyopic subjects with an aspheric multifocal back surface RGP contact lens (age range: 45 to 68 years). Reading additions ranged from +0.75 D to +2.50 D. Subjects were assessed initially and at 2, 6, and 12 weeks for ocular changes, visual performance, and subjective responses. RESULTS: We required 116 RGP lenses to achieve an acceptable fit and visual acuity in 28 subjects (55 eyes). At the final visit, the distance logMAR acuity with the multifocal contact lens (+0.12 +/- 0.10) was not statistically different (t = -0.623, P = -0.5388) from spectacle acuity at the initial visit (+0.10 +/- 0.12). The near logMAR acuity with the multifocal contact lens at the final visit (0.36 +/- 0.12) was not statistically different from that for near acuity with spectacles at the initial visit (0.33 +/- 0.13). No slit lamp signs worsened during the study. A reduction in myopia of 0.67 D was noted by the final visit. Spectacle blur was noted if the acuity at the initial refraction was compared to the acuity with the same refraction at the final visit (t = -3.287, P = 0.0028) but not when the refractive changes were incorporated (t = 1.058, P = 0.3127). All subjects rated the performance of the lenses very highly: comfort, 86%; distance acuity, 83%; near acuity, 73%; and stability of vision, 74%. Twenty-four subjects (86%) chose the multifocal contact lens as their preference. CONCLUSION: We demonstrated that a multifocal design is able to provide acceptable distance and near correction for presbyopic patients. The aspheric geometry required can be optimized for a given patient by considering his/her degree of ametropia, as well as the corneal topography.
Aged↗
Protection against ascending infection of the genital tract by Chlamydia trachomatis is associated with recruitment of major histocompatibility complex class II antigen-presenting cells into uterine tissue.
A mouse model of ascending infection following intravaginal inoculation with a strain of Chlamydia trachomatis isolated from humans has been used to identify immune mechanisms associated with protection against genital infection. BALB/c and C3H mice differed in their susceptibilities to infection and inflammatory disease. In both mouse strains, ascension of the organism and recruitment of bone marrow-derived mononuclear leukocytes were evident in uterine tissue 1 week postinfection. By 3 weeks the organism had been cleared and inflammation had been resolved in the BALB/c mice, but both persisted in the C3H animals. In athymic nude BALB/c mice both the organism and inflammation persisted, indicating the influence of the hosts' immune response on the outcome of infection. Both BALB/c and C3H mice had a Th1 response in draining lymph nodes, with predominant production of gamma interferon and tumor necrosis factor alpha, low levels of interleukin-10, and no detectable levels of interleukin-4. However, the composition of the early uterine infiltrate differed in these two mouse strains. Cell surface labeling and analysis of light scatter properties by flow cytometry identified a population of large, CD45(+) major histocompatibility complex class II mononuclear cells, which were a prominent feature of the infiltrates in BALB/c mice but were present in significantly lower numbers in C3H mice. These cells expressed the costimulatory molecules CD86 and CD40 and stimulated allogeneic T cells, suggesting that these mononuclear cells are a population of antigen-presenting cells and that they may play a role in clearing antigen and protecting against inflammatory disease in BALB/c mice. An additional level of immunological control may thus exist in genital chlamydial infection.
Animals↗
An evaluation of rectal mucosal proliferation measure variability sources in the polyp prevention trial: can we detect informative differences among individuals' proliferation measures amid the noise?
We assessed components of total variability of bromodeoxyuridine (BrdUrd) and proliferating cell nuclear antigen (PCNA) assays of rectal mucosal proliferation in a subset of 390 participants from the U. S. National Cancer Institute's multicenter Polyp Prevention Trial. Biopsies were blindly double-scored by two technicians. For those participants for whom at least one evaluable biopsy was obtained, a mean of 2.0 and 2.6 biopsies, and 6.2 and 8.7 crypts/biopsy were evaluated, respectively, with the BrdUrd and PCNA assays. Factors such as clinical center, scorer, and month of biopsy collection significantly affected the observed values of the labeling index (LI) and proliferative height (PH). Therefore, it is essential to control or adjust for these variables in proliferation studies. Sources of random variation for LI and PH measures remaining after the aforementioned factors include between-participant variation and several sources of within-participant variation, including variation over time, between biopsies, and between multiple measurements on the same biopsy. Both LI and PH measurements exhibited substantial variability over time, between biopsies, and from reading-to-reading of the same biopsy. When other sources of variability have been accounted for, the PCNA LI seems to have little between-participant variation. This brings into question its utility as a marker in colorectal cancer studies. The PCNA PH showed significant between-participant variability and may hold some promise as a useful marker in colorectal cancer studies. Results for BrdUrd were less conclusive. The BrdUrd LI showed marginally significant between-participant variation, whereas the corresponding variation for PH was nonsignificant.
Adult↗
Non-compliance in optometric practice.
The purposes of this paper is to explore how some of the recent and future changes relating to the optometric profession could affect non-compliant behaviour among patients. Non-compliance has been widely documented and discussed in numerous health care fields and is understood to be the responsibility of both the practitioner and patient working in a health care partnership. At least one third of patients have been reported to be non-compliant with health care recommendations which can result in the poor outcome of a treatment, secondary medical problems, dissatisfaction, frustration and the wasting of health resources. In recent years contact lens complications have been linked with non-compliant behaviour with contact lens care and maintenance regimens which has led to several media scares over contact lens related hygiene risks and has heightened interest in the issue of non-compliance in the field of optometry. Shared care schemes have already been adopted in some areas of the United Kingdom and if therapeutic pharmaceutical agents are introduced to the list of drugs permitted for use by optometrists in the future the issue of non-compliance will become even more poignant. Every optometrist needs to be aware of the high probability of non-compliant behaviour among patients, the consequences of this non-compliance and the steps that can be taken to enhance compliance in different areas of eye-care.
Contact Lenses↗
Applications of anion chromatography in terrestrial environmental research.
Ion chromatography can be applied to characterise single samples for a wide range of ionic species, at elevated or trace concentrations, or with automation may be used to determine many of the common ions on several thousand samples per year. It has been applied to a wide range of sample types of environmental interest. Examples of applications are given for the common sample types, i.e. atmospheric gases and particulates, water, biological materials and soil. The recent literature in the field of anion chromatography, as applied to environmental research, is reviewed (102 references). Suppressed and non-suppressed systems are covered, as are comparisons with other methods of analysis. Development of sample preparation methods, stationary and mobile phases, detection systems and techniques are also discussed.
Chromatography, Ion Exchange↗
A prospective study of the effect of education on non-compliant behaviour in contact lens wear.
The contact lens practitioner and patient present a specific case for the study of non-compliance in areas such as hygiene, solution use, appointment attendance and wearing times. Education is one of the factors thought to influence compliance among patients in general health care situations and contact lens practitioners are encouraged to educate patients in the care and maintenance of contact lenses. A prospective, randomized, controlled and double masked study was performed to assess the effect of a 'compliance enhancement strategy' on levels of compliance among contact lens wearers over twelve months. Eighty experienced contact lens patients were randomly allocated to two experimental groups. A standard level of contact lens instruction was applied to the first group and in addition the compliance enhancement strategy was applied to patients assigned to the second group. The strategy consisted of extra education for patients using a video, booklets, posters, a checklist and a health care contract. Patients were given free supplies of ReNu multipurpose solution and Medalist 38 soft contact lenses (Bausch and Lomb, Rochester, New York). Compliance levels were assessed at a twelve month aftercare appointment by demonstration and questionnaire. The results indicate that the compliance enhancement strategy had little significant effect on the compliance levels of the patients to who it was applied. The population of contact lens wearers were generally very compliant and the contact lenses and care regimen were clinically successful. The possibility that the assessment of non-compliance was not adequately sensitive to highlight small differences in non-compliant behaviour is discussed. The standard level of education applied to this sample of contact lens patient were adequate to ensure generally high levels of compliance with the simple care and maintenance regimen recommended.
Adolescent↗
Perinatal HIV infection and the effect of zidovudine therapy on transmission in rural and urban counties.
OBJECTIVES: To assess health care providers' identification of human immunodeficiency virus (HIV)-exposed infants, to ascertain the prevalence of transplacental or oral zidovudine treatment among infants exposed to HIV, and to estimate the impact of zidovudine use on perinatal transmission in rural and urban North Carolina. DESIGN: Survey of North Carolina newborns tested for HIV infection in 1993 and 1994 compared with the number of anonymous HIV-positive childbearing women. SETTING: North Carolina hospitals, public health clinics, and private physicians' offices. MAIN OUTCOME MEASURES: Rates of identification of HIV-exposed infants and of perinatal HIV-1 transmission, determined by HIV culture and polymerase chain reaction testing in the infants. RESULTS: The proportion of HIV-exposed children in North Carolina who were identified and tested increased from 60% in 1993 to 82% for all of 1994, and to more than 90% for the last quarter of 1994. The HIV-exposed infants born in rural counties were more likely to be recognized than those born in urban counties (P<.001). In 1994, most infants were evaluated relatively early in life: 39% by 1 week of age, 63% by 6 weeks, and 76% by 3 months. Among infants with recognized HIV exposure, transmission decreased significantly between 1993 and 1994, from 21% to 8.5%, respectively (P=.009). After the announcement of the results of the AIDS Clinical Trials Group Protocol 076, zidovudine was given to 75% of HIV-positive women who delivered infants in North Carolina. Only 5.7% of infants who received any zidovudine became infected, compared with 18.9% of infants who received no zidovudine (P=.007). CONCLUSIONS: Health care providers in North Carolina are identifying most of the state's HIV-seropositive pregnant women, treating them with zidovudine, and testing their infants soon after birth for HIV infection. The use of zidovudine in pregnant women and their infants has reduced perinatal HIV transmission in the state.
AIDS Serodiagnosis↗
Allium vegetables: their role in the prevention of cancer.
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Allium↗
Reproducibility of the measurement of colonic proliferation using bromodeoxyuridine across laboratories.
Although measures of colonic cell proliferation are being used as potential intermediate markers in chemoprevention studies, measurement standardization is still ongoing. This study was designed to assess the reproducibility of the labeling index quantification, as measured by bromodeoxyuridine, across four laboratories experienced in its use. Each institution submitted 10 slides, with one circled area of each slide to be scored. Each site followed its standard procedures for scoring colonic crypts; no attempts to standardize these procedures were made. There was high concordance among the laboratories on whether scorable crypts were present on a particular slide, but only two pairs of laboratories demonstrated agreement statistically greater than that predicted by chance. The overall difference among the sites on the number of scorable crypts was marginally significant (P = 0.083), and there was a highly significant overall difference in the magnitude of the labeling index (P < 0.0001). Sites 1 and 2 tended to have similar results, as did sites 3 and 4, most likely due to common training. Even with these discrepancies, high correlation (r > 0.75) was observed among the reported labeling index values for each pair of laboratories. Without standardized training, these laboratories may differ in the crypts considered appropriate for counting and in whether cells are counted as labeled or unlabeled. These results suggest that standardized training in scoring across all sites performing labeling index determinations is required to assure reproducibility across sites or studies. These results may also help explain discrepancies in the average values of the labeling index reported in the literature.
Analysis of Variance↗
Production of a biologically active recombinant teleostean growth hormone in E. coli cells.
We have isolated and characterized several recombinant lambda phage clones carrying growth hormone (GH) cDNA of striped bass (Morone saxatilis). Nucleotide sequence and the predicted amino acid sequence of sbGH was determined from a recombinant clone carrying the longest cDNA insert. The sbGH cDNA encodes a pre-hormone of 204 amino acid residues. Comparison of the predicted amino acid sequence of sbGH with those of other vertebrates revealed different degrees of sequence identity: approximately 98% with European sea bass; 90% with bluefin tuna; bonito and red seabream; 71% with winter flounder; 64% with salmonids; 55% with carp; and 38% with human. Expression of the mature sbGH cDNA (without the signal peptide sequence) in E. coli cells under regulation of the lambda phage PL promoter produced a polypeptide of 20 kDa. Following renaturation, this recombinant hormone was shown to be biologically active in a radioreceptor competition binding assay and in the induction of hepatic insulin-like growth factor I (IGF-I) mRNA synthesis in vivo.
Amino Acid Sequence↗
Treating the patient who is disfigured by head and neck cancer.
A 46-year-old man with laryngeal carcinoma was admitted to the medical service for lethargy. The medical team requested a psychiatric consultation to assist with the patient's depression, substance abuse, and noncompliance. The case is presented and discussed with reference to the issues of depression, disfigurement, dysfunction, and substance abuse in the patient with head and neck cancer.
Alcoholism↗
Antagonistic role of vitamin D3 and retinoic acid on the differentiation of chicken hematopoietic macrophages into osteoclast precursor cells.
An in vitro culture model of osteoclast differentiation is described which is derived from homogeneous populations of chick yolk sac and peripheral blood macrophages. In primary cultures, both types of macrophages undergo a proliferative phase, become quiescent after reaching high cell densities, then aggregate and eventually form large multinucleated giant cells (MNGCs), presumably by fusion. These MNGCs can be characterized as premature osteoclasts on the basis of several morphological and biochemical criteria, although they do not undergo the final differentiation step rendering them competent to resorb bone in vitro. Clonal analysis of single cell-derived colonies indicates that all macrophages have the potential to differentiate into these osteoclast-like cells under these culture conditions. Both retinoic acid and 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] modulate macrophage growth, but in an antagonistic manner. Although retinoic acid strongly promotes macrophage proliferation and impedes MNGC formation, 1,25-(OH)2D3 inhibits proliferation and changes the kinetics of MNGC formation. Combination experiments reveal that the proliferative signals induced by retinoic acid can override the signal to differentiate induced by 1,25-(OH)2D3. Our results indicate that even though retinoic acid and vitamin D3 act through homologous receptors, they have dramatically opposing effects on macrophage differentiation toward osteoclast progenitors.
Animals↗
Multinucleated cells can continuously generate mononucleated cells in the absence of mitosis: a study of cells of the avian osteoclast lineage.
The multinucleated bone-resorbing osteoclast has a hematopoietic origin. We have demonstrated previously that osteoclasts are derived from the monocytic lineage by fusion of mononuclear macrophage precursors. Using an in vitro-osteoclast differentiation model derived from pure populations of chick macrophage cultures, osteoclast-like multinucleated giant cells (MNGCs) can be formed by fusion following an active proliferation phase. However, after reaching a peak with 70% of the culture being MNGCs, a new round of expansion of the mononuclear cells is observed. The following experiments suggest that these mononuclear cells were derived directly from the MNGCs by a budding process, selectively from the central zone of the apical surface. After microinjection of the membrane-impermeable probe, Lucifer Yellow, into single MNGCs, initially only diffuse fluorescence, limited to the whole MNGC injected, was observed. However, after 24-48 hours fluorescent mononuclear cells were observed adjacent but distinct from the injected MNGC. To confirm that these mononuclear cells were indeed derived from a parent MNGC, single MNGCs were cloned into single wells. Within a week, the MNGC was surrounded by mononuclear cells, which eventually populated the entire well. These mononuclear cells could then give rise to a second generation of MNGCs following a three-week period of culture. To determine whether this process required mitosis, MNGCs were cultured for three days in the presence of the mitotic inhibitor, Ara-C, prior to microinjection with Lucifer Yellow. Fluorescent mononuclear cells were still seen to arise from a single injected MNGC under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗