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Biomedical subjects

D Anderson

Publications and source records attributed to D Anderson.

At least 307 records · Page 17Linked to original sources

Influence of in utero diethylstilbestrol exposure on the prognosis and biologic behavior of vaginal clear-cell adenocarcinoma.

Most young women with clear-cell adenocarcinoma (CCA) of the vagina have a history of prenatal exposure to diethylstilbestrol (DES). Some, however, develop vaginal CCA without a prior history of DES exposure. We hypothesized that the natural history of DES-exposed vaginal CCA and DES-unexposed vaginal CCA may differ. Cases were identified from the Registry for Research on Hormonal Transplacental Carcinogenesis which maintains information on cases of CCA of the lower genital tract occurring in women born after 1940. Four hundred and thirty-one cases satisfied FIGO criteria for primary vaginal carcinoma of which 318 had prenatal, hospital, obstetrician, or pharmacy records available for review. Of these, 80% (255/318) had written documentation of prenatal exposure to DES (DES+) and 20% (63/318) had no evidence of DES exposure (DES-) in their medical records. DES exposure was undetermined in 113 cases due to lack of appropriate medical records. Among cases with documentation, DES exposure was not associated with mean age at diagnosis, (DES+, 20.3 years, DES-, 21.1 years), stage (stage I: DES+, 59%, DES-, 54%; stage II: DES+, 32%, DES-, 33%; stage III: DES+, 7%, DES-, 11%; stage IV: DES+, 2%, DES-, 2%, mean tumor diameter or surface area, grade, histology, cell type, or initial therapy. Among cases which underwent pelvic and paraaortic lymph node sampling (DES+, 63%; DES-, 56%; P = NS) the prevalence of pelvic node involvement was similar (DES+, 18.6%; DES-, 17.1%). However, only 1.2% (2/161) of DES+ cases had positive paraaortic lymph nodes compared to 8.6% (3/35) of DES- cases (P = 0.041). Survival differed significantly between the two groups. Probability of survival at 5 and 10 years for DES+ cases was 84 and 78%, respectively, compared to 69 and 60%, respectively, for DES- cases (5 years, P = 0.007, and 10 years, P = 0.008). Presently, 21% (53/255) of DES+ cases are known to have died, compared to 37% (23/63) of DES- cases (P = 0.008). Sites of disease recurrence also differed. DES- cases were more likely than DES+ cases to present with or to later develop distant tumor to the lungs (24% vs 9%; P = 0.002) or metastases to supraclavicular lymph nodes (8% vs 1.6%; P = 0.017). Among the 113 cases with an uncertain history of DES exposure, survival was intermediate between the well-documented cases (79% at 5 years and 65% at 10 years with 35/113 or 31% known dead), as was frequency of metastases to the lungs (13%) or supraclavicular lymph nodes (5.3%).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma, Clear Cell↗

A comparison of four PTSD measures' convergent validities in Vietnam veterans.

We compared the convergent validities of four commonly used post-traumatic stress disorder (PTSD) measures in 80 help-seeking Vietnam veterans by contrasting their intercorrelations. When scored as continuous severity or frequency measures, the Mississippi Scale for Combat-related PTSD's and the Post-Traumatic Stress Disorder Interview's (PTSD-I's) concordances with other measures were similar to one anothers' and generally larger than those of either the Diagnostic Interview Schedule (DIS) PTSD module or the MMPI PTSD scale. However, when used only to identify stress disorder's presence or absence, the four techniques' concordances were nearly identical. This suggested that the four measures have similar convergent validities when used simply to identify PTSD, but that the PTSD-I and Mississippi scale offer better convergent validity than the MMPI or DIS instruments when used as severity measures.

Adult↗

Systemic lymphadenopathic histology in human immunodeficiency virus-1-seropositive drug addicts without apparent acquired immunodeficiency syndrome.

We examined lymph nodes from multiple sites in 50 individuals infected with human immunodeficiency virus (HIV-1) who died accidentally of drug overdoses and in whom there was no evidence of opportunistic infection. The size, histologic pattern, presence of Warthin-Finkeldey-type giant cells, and estimation of CD4 cell count of these lymph nodes were compared with those of 13 seronegative drug addicts (controls). Lymph nodes from seropositive individuals were slightly but significantly larger than those of controls. Lymph nodes from seropositive cases were much more likely to contain secondary follicles (90%) than were those from controls (20%). Unlike follicles in control nodes, most secondary follicles in the seropositive cases were in various stages of fragmentation and involution. As follicular changes progressed, there was a decrease in CD4 cells and an increase in intrafollicular and paracortical plasma cells. Plasmacytosis was much more prevalent in lymph nodes from seropositive individuals than in controls. Warthin-Finkeldey-type giant cells were present in at least one node in 29 of 50 seropositive cases, were most numerous in those showing follicular hyperplasia with fragmentation (45% of cases), and were especially numerous in Peyer's patches (61% of cases). There was generally good concordance of HIV-1-associated follicular morphology among diverse lymph node groups. There is prolonged generalized, mild hyperplastic lymphadenopathy with frequent syncytial cells in intravenous drug addicts with asymptomatic HIV-1 infection.

AIDS-Related Complex↗

Report from the working group on the in vivo mammalian bone marrow chromosomal aberration test.

The following summary represents a consensus of the working group, except where noted. The goal of this working group was to identify the minimal requirements needed to conduct a scientifically valid and practical in vivo chromosomal aberration assay. For easy reference, the items discussed are listed in the order in which they appear in OECD guideline 475. Specific disagreement with the current and/or proposed OECD guideline is presented in the text. Introduction, purpose, scope, relevance, application, and limits of test: This test would not be appropriate in situations where there was sufficient evidence to indicate that the test article or reactive metabolites could not reach the bone marrow. Test substances: Solid and liquid test substances should be dissolved, if possible, in water or isotonic saline. If insoluble in water/saline, the test substance should be dissolved or homogeneously suspended in an appropriate vehicle (e.g., vegetable oil). A suspension was not considered suitable for an intravenous injection. The use of dimethyl sulfoxide as an organic solvent was not recommended. The use of any uncommonly used solvent/vehicle should be justified. Freshly prepared solutions or suspensions of the test substance should be employed unless stability data demonstrate the acceptability of storage. Selection of species: Any commonly used rodent species was deemed acceptable but rats or mice were preferred, with no strain preference. Number and sex: A consensus could not be reached as to the requirement for both sexes versus one sex in this assay. It was suggested that a single sex should be used unless pharmacokinetic and/or toxicity data indicated a difference in metabolism and/or sensitivity between males and females. The size of the experiment (i.e., number of cells per animal, number of animals per treatment group) should be based on statistical considerations. Lacking a formal analysis, it was agreed that at least 100 metaphase cells should be scored per animal while at least five animals of any one sex should be evaluated per treatment group. Recently, a formal analysis of the numbers of cells to score per animal and numbers of animals to score per treatment group was conducted at a workshop on statistics for in vivo mutagenicity tests (Adler et al., 1994). The conclusion of this workshop was that, based on a type I error of 0.05 and a power of 80% to detect at least a doubling in the control frequency, the minimal number of cells to score per animal was 200 and the minimal number of animals to score per sex per treatment group was four.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

In vivo rodent erythrocyte micronucleus assay.

The following summary represents a consensus of the working group except where noted. The items discussed are listed in the order in which they appear in the OECD guideline (474) for easy reference. Introduction, purpose, scope, relevance, application and limits of test. The analysis of immature erythrocytes in either bone marrow or peripheral blood is equally acceptable for those species in which the spleen does not remove micronucleated erythrocytes. In the mouse, mature erythrocytes are also an acceptable cell population for micronucleus analysis when the exposure duration exceeds 4 weeks. Test substances. Organic solvents such as DMSO are not recommended. Freshly prepared solutions or suspensions should be used unless stability data demonstrate the acceptability of storage. Vegetable oils are acceptable as solvents or vehicles. Suspension of the test chemicals is acceptable for p.o. or i.p. administration but not for i.v. injection. The use of any unusual solvent should be justified. Selection of species. Any commonly used laboratory rodent species is acceptable. There is no strain preference. Number and sex. The size of experiment (i.e., number of cells per animal, number of animals per group) should be finalized based on statistical considerations. Although a consensus was not achieved, operationally it was agreed that 2000 cells per animal and four animals per group was a minimum requirement. In general, the available database suggests that the use of one gender is adequate for screening. However, if there is evidence indicating a significant difference in the toxicity between male and female, then both sexes should be used. Treatment schedule. No unique treatment schedule can be recommended. Results from extended dose regimens are acceptable as long as positive. For negative studies, toxicity should be demonstrated or the limit dose should be used, and dosing continued until sampling. Dose levels. At least three dose levels separated by a factor between 2 and square root of 10 should be used. The highest dose tested should be the maximum tolerated dose based on mortality, bone marrow cell toxicity, or clinical symptoms of toxicity. The limit dose is 2 g/kg/day for treatment periods of 14 days or less and 1 g/kg/day for treatment periods greater than 14 days. A single dose level (the limit dose) is acceptable if there is no evidence of toxicity. Controls. Concurrent solvent (vehicle) controls should be included at all sampling times. A pretreatment sample, however, may also be acceptable only in the short treatment period peripheral blood studies. A concurrent positive control group should be included for each experiment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Comparison of biphasic and monophasic waveforms in epicardial atrial defibrillation.

OBJECTIVES: Because biphasic waveforms have previously been shown to be more efficient than monophasic waveforms in defibrillation of the ventricle, we compared the efficiency of the two waveforms in defibrillation of the atria. BACKGROUND: The development of an implantable atrial defibrillator would offer significant advantages over current approaches to the management of atrial fibrillation. Patient tolerance of atrial shocks from such a device, however, would depend critically on the deployment of an efficient waveform. METHODS: Both the monophasic and biphasic shocks were of 8-ms duration, and the biphasic was a dual-capacitor waveform with equal first- and second-phase duration and leading-edge voltage. One hundred randomized atrial shocks were evaluated in 21 patients during cardiopulmonary bypass. Atrial fibrillation was induced by the application of alternating current. Atrial shocks were delivered through customized, contoured epicardial paddles applied to the posterior left atrial wall (surface area 11 cm2) and to the anterior right atrial wall (surface area 26 cm2). RESULTS: For the monophasic waveform the delivered energy (joules) associated with 50% success (E50) was 1.44 J (95% confidence interval [CI] 0 to 11.2) and with 80% (E80) success 3.9 J (95% CI 2.42 to 109.8); for the biphasic waveform 50% success was achieved with 0.37 J (95% CI 0.36 to 0.38) (p = NS) and 80% success with 0.57 J (95% CI 0.56 to 0.58) (p < 0.05). CONCLUSIONS: A biphasic waveform is more efficient than a monophasic waveform in atrial defibrillation. This may have implications for the development of an implantable atrial defibrillator for paroxysmal atrial fibrillation in addition to improvement of elective transthoracic and endocardial cardioversion of chronic atrial fibrillation.

Aged↗

L-carnitine via enzyme-catalyzed oxidative kinetic resolution.

L-Carnitine of high optical purity was prepared via kinetic resolution using a mutant strain of Acinetobacter calcoaceticus ATCC 39647. This organism preferentially metabolized the D-enantiomer of the racemate to furnish L-carnitine. Recovery of L-carnitine was 93%, providing a total weight yield of 46.5% in 92% enantiomeric excess. The mode of degradation of carnitine was shown to proceed via a monooxygenase-catalyzed oxidative cleavage resulting in the formation of trimethylamine and malic acid. The data suggest that the stereoselective metabolism of DL-carnitine is probably the result of differential permeability of the cell membrane towards the optical antipodes.

Acinetobacter calcoaceticus↗

The bacteriophage phi 29 head-tail connector shows 13-fold symmetry in both hexagonally packed arrays and as single particles.

The symmetry of the phi 29 head-tail connector is controversial: several studies of two-dimensional arrays of the connector have found a 12-fold symmetry, while a recent study of isolated particles has found a 13-fold symmetry. To investigate whether a polymorphism of the structure might explain these different results, electron microscopy and image analysis were used to study both isolated connectors and particles in hexagonally packed arrays. The hexagonally packed arrays have a P1 symmetry, and the connectors displayed 13 subunits both in the arrays and as isolated single particles. While we do not observe a polymorphism between connectors in two-dimensional arrays and as isolated particles, data show that the connectors can exist with either 12 or 13 subunits. A three-dimensional reconstruction of our 13-fold connector was generated by combining an averaged side-view projection with the known symmetry. The structure of rosettes of the connectors formed in the presence of phi 29 prohead RNA (pRNA) was also examined. These rosettes contain five connectors arranged about a single connector in the center, and this arrangement may reflect an essential role of the pRNA in mediating a symmetry mismatch between either a 12- or 13-fold symmetric connector and a putative fivefold symmetric prohead portal vertex into which the connector fits.

Bacillus Phages↗

Snoring: is it in the ear of the beholder?

Complaint of snoring, which is usually voiced by a patient's bedpartner, frequently leads to investigations in the sleep laboratory that are designed to assess snoring objectively and determine whether it is a symptom of sleep apnea. How well this subjective complaint of the listener is confirmed by the objective measurement of snoring is not known. Consequently, we designed a study i) to test the validity of self-perception of snoring and ii) to compare subjective perception of snoring by the sleep technologist with objective measurement of its frequency and loudness. We studied 613 unselected patients referred to our sleep clinic because of snoring and suspicion of sleep apnea. They all had nocturnal polysomnography that included measurements of snoring, expressed as the number of snores per hour of sleep [snoring index (SI)] and mean (dBmean) and maximum (dBmax) nocturnal sound intensity. Following the sleep study, the technologist (and patient) independently rated a patient's snoring as none, mild, moderate or severe. Kruskall-Wallis test, Spearman rank correlations and Cohen's kappa statistics were used to compare the groups, examine the correlations between subjective and objective measurements, and check the agreement between them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

BQ123, an ETA-receptor antagonist, attenuates hypoxic pulmonary hypertension in rats.

To investigate the role of endothelin-1 (ET-1) in the pathogenesis of hypoxic pulmonary hypertension, we studied the effects of a recently described endothelin-receptor antagonist (ETA), BQ123, on the development of this process. Intraperitoneal osmotic pumps were placed into 8-wk-old Sprague-Dawley rats that received either saline or BQ123 (0.15 mg/h). The rats were maintained in room air normoxia or placed in a hypobaric chamber (380 Torr) for 2 wk to induce hypoxic pulmonary hypertension. There were no hemodynamic differences between normoxic rats treated with either saline or BQ123. However, treatment with BQ123 attenuated the hypoxia-induced increase in pulmonary arterial mean pressure and total pulmonary resistance index by 60 and 87% respectively. There was also a reduction in hypoxia-induced right ventricular hypertrophy in the BQ123 group. Histological studies performed using a barium-gelatin fixation technique in hypoxic BQ123-treated animals demonstrated a decrease in medial wall thickness in arteries corresponding to the respiratory and terminal bronchioles, respectively. Similarly, there was a significant reduction in the degree of muscularization of more distal vessels at the level of alveolar ducts in BQ123-treated hypoxic rats. We conclude that the ETA-receptor antagonist BQ123 attenuates the development of hypoxic pulmonary hypertension in rats in vivo, thereby suggesting a possible contributing role for ET-1 and the ETA receptor in the pathogenesis of this process.

Animals↗

XASH genes promote neurogenesis in Xenopus embryos.

Neural development in Drosophila is promoted by a family of basic helix-loop-helix (bHLH) transcription factors encoded within the Achaete Scute-Complex (AS-C). XASH-3, a Xenopus homolog of the Drosophila AS-C genes, is expressed during neural induction within a portion of the dorsal ectoderm that gives rise to the neural plate and tube. Here, we show that XASH-3, when expressed with the promiscuous binding partner XE12, specifically activates the expression of neural genes in naive ectoderm, suggesting that XASH-3 promotes neural development. Moreover, XASH-3/XE12 RNA injections into embryos lead to hypertrophy of the neural tube. Interestingly, XASH-3 misexpression does not lead to the formation of ectopic neural tissue in ventral regions, suggesting that the domain of XASH proneural function is restricted in the embryo. In contrast to the neural inducer noggin, which permanently activates the NCAM gene, the activation of neural genes by XASH-3/XE12 is not stable in naive ectoderm, yet XASH-3/XE12 powerfully and stably activates NCAM, Neurofilament and type III beta-tubulin gene expression in noggin-treated ectoderm. These results show that the XASH-3 promotes neural development, and suggest that its activity depends on additional factors which are induced in ectoderm by factors such as noggin.

Animals↗

Influences on the use of capital by public hospitals.

This paper examines key influences on the volume of capital employed by public hospitals. Empirical models are constructed and analysed separately for total capital employed and for plant and equipment only, using data from 68 Victorian hospitals. Such data provide an empirical base to guide government decisions on funding capital expenditure in hospitals. The analysis finds that the proportion of hospital expenditure devoted to outpatients and teaching, and the proportion of funding derived from government all influence the level of capital utilised per inpatient. The model provided a reasonable fit for plant and equipment, but much improved data coverage and consistent valuation of land and buildings are required to adequately explain influences on total capital.

Ambulatory Care↗

Amaurosis fugax: prognosis and the role of acetylsalicylic acid.

Amaurosis fugax has been grouped together with other forms of transient ischemic attacks (TIAs) in the neurologic literature in analyses of prognosis. Although episodes of transient visual loss (TVL) are presumed to be due to ischemia, the prognosis with respect to subsequent stroke and myocardial infarct (MI) appears to differ from cerebral TIAs. We reviewed the clinical course of 73 patients above the age of 45 years who presented to our clinics with a distinct history of TVL. With an average follow-up period of 38 months, the incidence rates of cerebrovascular accident, cerebral TIA and MI following presentation with TVL were 1%, 4% and 7% respectively. Although there was a trend toward fewer episodes of amaurosis with use of acetylsalicylic acid (ASA), the difference was not statistically significant. In addition, ASA did not appear to offer a benefit with respect to future ischemic events. Patients with monocular TVL appeared more likely to experience a TIA, whereas those with binocular TVL appeared more likely to experience an MI.

Aged↗

CD30 antigen, a marker for Hodgkin's lymphoma, is a receptor whose ligand defines an emerging family of cytokines with homology to TNF.

CD30 is a surface marker for neoplastic cells of Hodgkin's lymphoma and shows sequence homology to members of the tumor necrosis factor (TNF) receptor superfamily. Using a chimeric probe consisting of the extracellular domain of CD30 fused to truncated immunoglobulin heavy chains, we expression cloned the cDNA cognate from the murine T cell clone 7B9. The encoded protein is a 239 amino acid type II membrane protein whose C-terminal domain shows significant homology to TNF alpha, TNF beta, and the CD40L. Cross-hybridization to an induced peripheral blood T cell cDNA library yielded the human homolog, which is 72% identical at the amino acid level. The recombinant human ligand enhances the proliferation of CD3-activated T cells yet induces differential responses, including cell death, in several CD30+ lymphoma-derived clones. The human and murine genes map to 9q33 and the proximal region of chromosome 4, respectively.

Amino Acid Sequence↗