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PubMed1997

Rapid screening assay for anti-GBM antibody and ANCAs; an important tool for the differential diagnosis of pulmonary renal syndromes.

BACKGROUND: Pulmonary renal syndrome is encountered in several diseases such as Goodpasture's syndrome, antineutrophil cytoplasmic antibody (ANCA) associated systemic vasculitis, systemic lupus erythematosus (SLE) and infection-associated or drug-induced glomerulonephritis. To preserve organ function it is of vital importance to make the correct diagnosis and institute adequate therapy early, in the acute phase. METHOD: An enzyme-linked immunosorbent assay (ELISA), specially designed as a rapid screening assay for antiglomerular basement membrane (anti-GBM) antibody, proteinase-3 (PR3-) ANCA and myeloperoxidase-(MPO-) ANCA were evaluated from 1060 serum samples drawn from patients with clinically suspected pulmonary renal syndrome or rapidly progressive glomerulonephritis (RPGN). RESULTS: Of the 1060 serum samples, 142 were positive for anti-GBM antibody (n = 19), PR3-ANCA (n = 60), or MPO-ANCA (n = 73). Of the 142 samples, 10 were double positive. Reanalysis of positive sera with a quantitative ELISA yielded results manifesting good correlation with those of the the rapid screening assay. Of 918 sera found to be negative in the rapid screening assay, 105 were also tested with IIF, 11 being found to be positive. However, these 11 sera manifested no specificity for PR3 or MPO, but some were specific for bactericidal/permeability-increasing proteins, lactoferrin or elastase ANCAs. Two of the patients whose sera yielded negative results in the rapid assay had systemic vasculitis. CONCLUSION: The ELISA thus detects the true antibodies to PR3, MPO, and GBM, whereas IIF detects additional specificities. The findings suggest the rapid assay results to be of high positive predictive value, and the assay to be of high diagnostic specificity and sensitivity and thus useful in the diagnostic workup in suspected cases of RPGN or pulmonary renal syndrome.

Anti-Glomerular Basement Membrane Disease↗
PubMed1984

Congenital malformations and maternal drinking water supply in rural South Australia: a case-control study.

A case-control study, carried out in the Mount Gambier region of South Australia, investigated the relationship between mothers' antenatal drinking water source and malformations in offspring. It was prompted by earlier descriptive findings of a statistically significant, and localized, increase in the perinatal mortality rate in Mount Gambier, due principally to congenital malformations affecting the central nervous system and multiple organ systems. Available for statistical analysis were 218 case-control pairs, from the period 1951-1979, individually matched by hospital, maternal age (+/- 2 years), parity and date of birth (+/- 1 month). Compared with women who drank only rainwater during their pregnancy (relative risk (RR) = 1.0), women who consumed principally groundwater had a statistically significant increase in risk of bearing a malformed child (RR = 2.8). Statistically significant risk increases occurred specifically for malformations of the central nervous system and musculoskeletal system. Reanalysis of the data by estimated water nitrate concentration demonstrated a nearly threefold increase in risk for women who drank water containing 5-15 ppm of nitrate, and a fourfold increase in risk for those consuming greater than 15 ppm of nitrate. A seasonal gradient in risk was evident among groundwater consumers, ranging from 0.9 for babies conceived in winter, 3.0 in autumn, to 7.0 and 6.3 for spring and summer conceptions, respectively. Linear logistic regression analysis, controlling for risk factors not accounted for in the study design, showed that maternal water supply, infant's sex, and mother's area of residence all contributed significantly to the risk of malformation. These results are discussed in relation to previous experimental and human descriptive studies, suggesting a plausible mechanism for nitrate-induced teratogenesis.

Abnormalities, Drug-Induced↗
PubMed1987

Do Atomic Veterans have excess cancer? New results correcting for the healthy soldier bias.

Reanalysis of the National Research Council report on Mortality of Nuclear Weapons Test Participants, released June 4, 1985, shows 62% excess cancer among soldiers involved in nuclear weapons testing in 1957 codenamed PLUMBBOB, who had exposures to fallout of 300 mrem or more. Although the "healthy soldier bias" was discussed in the original report and a method of correcting for it was described, false negative results were reported because no correction was actually made. Correcting for the healthy soldier bias reveals excess digestive, respiratory, leukemia, and other cancers in PLUMBBOB participants whose reported doses were over 300 mrem.

Dose-Response Relationship, Radiation↗
PubMedDate not supplied

A note on the human sex ratio and factors influencing family size in Japan.

A reanalysis of a set of data on the sex distribution of children in Japanese families shows that further increase in family-size is related to the sex of the second child (P less than 0.025). When the second child is male, there is a reduced likelihood of further children. This result is consistent with findings from a U.S. fertility study.

Family Characteristics↗
PubMedDate not supplied

Role of de Vries in the recovery of Mendel's work. I. Was de Vries really an independent discoverer of Mendel?

Recently, doubt has been cast on the view that de Vries developed the idea of disjunction independently of Mendel. Arguments are based on de Vries' own writings that showed the F2 data of his numerous crosses are reported as 3:1 ratios only after 1900. They also show that his theory of inheritance becomes quasi Mendelian only after 1900. The authors of this review paper cannot but agree with de Vries' critics that he did not develop his law of disjunction independently of Mendel. They also raise some questions that, hopefully, will lead to a reanalysis of de Vries' theory of inheritance in 1900.

Botany↗
PubMedDate not supplied

Coadaptation revisited.

During the four decades or more since Dobzhansky introduced the term "coadaptation" to refer to the commonly observed selective superiority of inversion heterozygotes in populations of Drosophila pseudoobscura, the definition of the term has evolved, as have views concerning the rapidity with which coadaptation might occur. Indeed, the paucity of demonstrated instances of linkage disequilibrium in natural populations has led many to dismiss coadaptation as a factor in evolutionary change. The present article reviews the reasons why coadaptation (and the equivalent expression, "integration of gene pools") was proposed as a phenomenon occurring in local (or experimental) populations, offers supporting data obtained through a reanalysis of data on irradiated populations of D. melanogaster, and concludes that sound evidence supports coadaptation as a factor in the genetic change of populations.

Adaptation, Biological↗
PubMed1996

Molecular evolutionary dynamics of cytochrome b in strepsirrhine primates: the phylogenetic significance of third-position transversions.

DNA sequences of the complete cytochrome b gene are shown to contain robust phylogenetic signal for the strepsirrhine primates (i.e., lemurs and lorises). The phylogeny derived from these data conforms to other molecular studies of strepsirrhine relationships despite the fact that uncorrected nucleotide distances are high for nearly all intrastrepsirrhine comparisons, with most in the 15%-20% range. Cytochrome b sequences support the hypothesis that Malagasy lemuriforms and Afro-Asian lorisiforms each comprise clades that share a sister-group relationship. A study (Adkins and Honeycutt 1994) of the cytochrome c oxidase subunit II (COII) gene placed one Malagasy primate (Daubentonia) at the base of the strepsirrhine clade, thereby suggesting a diphyletic Lemuriformes. The reanalysis of COII third-position transversions, either alone or in combination with cytochrome b third-position transversions, however, yields a tree that is congruent with phylogenetic hypotheses derived from cytochrome b and other genetic data sets.

Animals↗
PubMed1994

Voices of leadership in a community under stress: personal observations by officials on an epidemiologic mistake.

We studied the responses of leaders in a suburban community in western Canada near Edmonton, Alberta, that was affected by a false allegation of increased cancer risk. In 1986, a cancer agency responded to community concerns by conducting a study of cancer incidence (1979-1983) and reported elevations on the order of 25 per cent over expected for most sites. Reanalysis of these data several months later revealed an error in the population figure used to calculate the rates. Correction brought the rates into line with Alberta as a whole and comparable to those for other communities surrounding Edmonton. We interviewed elected and appointed public officials in one affected community as well as non-official community leaders and realtors to determine their subjective impression regarding the effect of the incident on their communities and to rule out alternative explanations for the drop in housing prices in association with the incident we have reported elsewhere. Their narrative responses were particularly interesting and articulate, and are quoted at length. Their collective perceptions appear to confirm the impression of a profound impact on the community, reflected in housing prices, and attribute at least part of the impact to the disclosure that a high official in the community was afflicted by cancer. Most felt that there remained a great deal of latent concern in the community and at least some felt that a subsequent public issue involving transmission line rights-of-way near the community reactivated this latent concern.

Adult↗
PubMed1989

Exogenous female hormones and rheumatoid arthritis: a methodological view of the contradictions in the literature.

The purpose of this review is not to resolve the contradictory findings that are present in the literature. Rather, it considers a selected number of issues that may pertain to some future understanding of the current controversy. Furthermore, certain issues such as biological plausibility and the absence of a definitive dose, duration, or timing relationships are not discussed. If the association of the use of exogenous female hormones with the prevention of rheumatoid arthritis came to be accepted as likely causal, basic scientists might well unravel the biological processes involved. The dose and duration of exposure to the hormones and the timing of the exposure (current use versus past use) in relation to the preventative effect remains unclear. While clearly a point against a causal relationship the possibility exists that this may result from errors in recall or that prior hormone exposure may 'vaccinate' a woman against the disease. A number of studies have been published only in abstract or are still underway. Reanalysis of existing data sets may also provide some insight into the contradictory findings. The issues raised in this review are of relevance to investigators. They may also be used by readers interested in this topic who wish to attempt to resolve the conflicts in the hormone-rheumatoid arthritis literature for themselves.

Arthritis, Rheumatoid↗
PubMed1991

Neuroleptics and the natural course of schizophrenia.

To determine if neuroleptic treatment changes the natural course of schizophrenia, 22 studies were reviewed in which relatively similar patients were or were not given neuroleptics at specific times during the course of their illness. Nineteen of the studies were from first- or predominantly first-break populations. While there was little consensus among the authors of the studies reviewed, a reanalysis of the data indicates that early intervention with neuroleptics in first-break schizophrenic patients increases the likelihood of an improved long-term course. This finding is similar to that of earlier investigators who indicated there was a decrease in patients with the more severe forms of the illness following the introduction of convulsive therapies. Furthermore, there is evidence that stable schizophrenic patients whose neuroleptics are discontinued and have relapses may have a difficult time returning to their previous level of function. The findings describe in this paper have implications for both the treatment of schizophrenia and for understanding the pathophysiological processes that determine the course of the disorder.

Antipsychotic Agents↗
PubMed2003

Thresholds of carcinogenicity in the ED01 study.

The results of the articles on the carcinogenicity of 2-acetylaminofluorene (J. H. Farmer et al., 1980, J. Environ. Pathol. Toxicol. 3, 55-68; N. A. Littlefield et al., 1980, J. Environ. Pathol. Toxicol. 3, 17-34) in approximately 25,000 female mice were reanalyzed by the procedure proposed earlier (W. J. Waddell, 2002, TOXICOL: Sci. 68, 275-279) using the Rozman scale (K. K. Rozman et al., 1996, Drug Metab. Rev. 28, 29-52). In contrast to some conclusions of the lack of a threshold for carcinogenesis that have been made in the past from this study, this reanalysis showed a clear and consistent threshold for bladder neoplasms at about 10 19.5 molecules/kg/day and for liver neoplasms at about 10 19.1 molecules/kg/day. The slopes of the dose-response curves for bladder neoplasms from 17 months through 33 months were consistently very steep, while those for liver neoplasms increased from a shallow slope at 18 months to a steep slope at 33 months. This is interpreted to indicate that the mechanism of carcinogenesis may be different in the two organs. A linear response for percentage tumors plotted against dose on a logarithmic scale is confirmed by this analysis, which is based on the fundamental principle that chemical potential effects a linear response. Furthermore, this application continues to show a sharp threshold for carcinogenesis. The implications of these observations should be important in the extrapolation of results from animal experiments to human risk assessment.

2-Acetylaminofluorene↗
PubMed1989

Sex preselection in rabbits: live births from X and Y sperm separated by DNA and cell sorting.

Intact, viable X and Y chromosome-bearing sperm populations of the rabbit were separated according to DNA content with a flow cytometer/cell sorter. Reanalysis for DNA of an aliquot from each sorted population showed purities of 86% for X-bearing sperm and 81% for Y-bearing sperm populations. Sorted sperm were surgically inseminated into the uterus of rabbits. From does inseminated with sorted X-bearing sperm, 94% of the offspring born were females. From does inseminated with sorted Y-bearing sperm from the same ejaculates, 81% of the offspring were males. The probability of the phenotypic sex ratios differing from 50:50 were p less than 0.0003 for X-sorted sperm and p less than 0.004 for Y-sorted sperm. Thus, the phenotypic sex ratio at birth was accurately predicted from the flow-cytometrically measured proportion of X- and Y-bearing sperm used for insemination.

Animals↗
PubMed1992

Dietary fatty acid thresholds and cholesterolemia.

Results obtained with cebus monkeys indicate that dietary myristic (14:0) and palmitic (16:0) acids exert disparate effects on cholesterol metabolism, whereas the ability of linoleic acid (18:2) to decrease total plasma cholesterol displays an upper limit or threshold. Reanalysis of published data suggests a similar situation pertains in humans. In agreement with an earlier human study, 14:0 appears to be the principal saturated fatty acid that raises plasma cholesterol whereas 18:2 lowers it. Oleic acid (18:1) appears neutral. The effect of 16:0 may vary. In normocholesterolemic subjects consuming diets containing less than or equal to 300 mg/day of cholesterol, 16:0 appears to be without effect on plasma cholesterol. However, in hypercholesterolemic subjects (greater than 225 mg/dl) and especially those consuming diets providing cholesterol intakes of greater than or equal to 400 mg/day, dietary 16:0 may expand the plasma cholesterol pool.

Animals↗
PubMed2005

Human muscle gene expression responses to endurance training provide a novel perspective on Duchenne muscular dystrophy.

Global gene expression profiling is used to generate novel insight into a variety of disease states. Such studies yield a bewildering number of data points, making it a challenge to validate which genes specifically contribute to a disease phenotype. Aerobic exercise training represents a plausible model for identification of molecular mechanisms that cause metabolic-related changes in human skeletal muscle. We carried out the first transcriptome-wide characterization of human skeletal muscle responses to 6 wk of supervised aerobic exercise training in 8 sedentary volunteers. Biopsy samples before and after training allowed us to identify approximately 470 differentially regulated genes using the Affymetrix U95 platform (80 individual hybridization steps). Gene ontology analysis indicated that extracellular matrix and calcium binding gene families were most up-regulated after training. An electronic reanalysis of a Duchenne muscular dystrophy (DMD) transcript expression dataset allowed us to identify approximately 90 genes modulated in a nearly identical fashion to that observed in the endurance exercise dataset. Trophoblast noncoding RNA, an interfering RNA species, was the singular exception-being up-regulated by exercise and down-regulated in DMD. The common overlap between gene expression datasets may be explained by enhanced alpha7beta1 integrin signaling, and specific genes in this signaling pathway were up-regulated in both datasets. In contrast to these common features, OXPHOS gene expression is subdued in DMD yet elevated by exercise, indicating that more than one major mechanism must exist in human skeletal muscle to sense activity and therefore regulate gene expression. Exercise training modulated diabetes-related genes, suggesting our dataset may contain additional and novel gene expression changes relevant for the anti-diabetic properties of exercise. In conclusion, gene expression profiling after endurance exercise training identified a range of processes responsible for the physiological remodeling of human skeletal muscle tissue, many of which were similarly regulated in DMD. Furthermore, our analysis demonstrates that numerous genes previously suggested as being important for the DMD disease phenotype may principally reflect compensatory integrin signaling.

Biopsy↗
PubMed1991

Electroencephalographic quantitation of opioid effect: comparative pharmacodynamics of fentanyl and sufentanil.

The authors compared the pharmacodynamics of sufentanil with those of fentanyl using the electroencephalogram (EEG) as a measure of opioid drug effect. Sixteen patients were given a rapid infusion of sufentanil (18.75 micrograms/min) during EEG recording. To quantitate the opioid-induced slowing of the EEG, the authors analyzed its power spectrum and calculated the spectral edge. An inhibitory sigmoid Emax model of the maximal decrease in spectral edge produced by the opioid related spectral edge values to serum concentrations of sufentanil. The resulting data for the pharmacodynamic parameters of sufentanil were compared with fentanyl parameters that were obtained by reanalysis from an identically conducted, previously published study. The half-time of blood-brain equilibration (T1/2Keo) was not statistically different between sufentanil and fentanyl (6.2 +/- 2.8 vs. 6.6 +/- 1.7 min, mean +/- SD, respectively). The intrinsic potency of sufentanil, as measured by the serum concentration needed to cause half the maximal EEG slowing (IC50), was 12-fold greater (0.68 +/- 0.31 ng/ml) than that of fentanyl (8.1 +/- 2.2 ng/ml). The second part of the study verified the hypothesis that administration of equipotent bolus doses would produce equal onset times. Bolus injections of either 125 micrograms of sufentanil or 1,250 micrograms of fentanyl were given during EEG recording. The time from injection to 50% maximal EEG slowing (T50) was calculated for each patient. The values for T50 for the two groups did not differ. The authors conclude that fentanyl and sufentanil have similar pharmacodynamic profiles, the former being 12 times more potent than the latter.

Adolescent↗
PubMed1980

VMA excretion in patients with pheochromocytoma.

Studies in 20 patients, and a reanalysis of previously published data demonstrate that there is a significant linear relationship between the rate of urinary excretion of 3-methoxy-4-hydroxymandelic acid and the size of a pheochromocytoma. This relationship is most significantly demonstrated in a small group of patients with bilateral adrenal disease as part of the MEN II syndrome. Since not all pheochromocytomas are accurately localized preoperatively and significant numbers can be bilateral or extra-adrenal, this predictive index of tumor size has useful surgical implications. An obvious discrepancy between a prediction of size and operative findings should alert the surgeon to a more thorough search of the opposite adrenal and, indeed, all extra-adrenal paraganglionic sites for other secreting tumor tissue.

Adrenal Gland Neoplasms↗
PubMed1984

Does surgery attract students who are more resistant to stress?

This article examines perceptions of stress and career choice. One hundred sixty-nine junior students specified what they thought were the two most and two least stressful careers, as well as their own career preferences before and after a 12-week surgical clerkship. The class was divided for analysis into three groups: those who selected careers that they said were A) most stressful (42%), B) least stressful (10%), and C) neither most nor least stressful (48%). Surgery was cited as one of the two most stressful choices by 99% of the class before and 93% after the clerkship. The next most stressful career was internal medicine, cited by 43% before and 35% after the clerkship. The two least stressful careers were dermatology and radiology, cited by approximately 50% of the class before and after the clerkship. Those who chose careers that they said were most stressful had significantly higher self-esteem (p less than 0.05), experienced less unfavorable stress themselves as measured by a 31-item stress scale before and after the clerkship (p less than 0.01), and experienced more favorable (in their view) stress (p less than 0.05) than did the other two groups. Reanalysis of data comparing those who selected surgery with those who did not confirmed findings similar to that of the matched high-stress career group. The study suggests that some students may be able to tolerate stress better and in fact, tend to thrive in an environment that they perceive as stressful, and that such students are more likely to go into a surgical career, which they foresee as one of the most stressful that they can enter.

Attitude of Health Personnel↗
PubMedDate not supplied

The utility and validity of the modified brief pain inventory in a multiple-dose postoperative analgesic trial.

OBJECTIVES: Patients undergoing major surgery often require several days of postoperative analgesia. However, few data exist on the longitudinal course of postoperative pain and the psychometric properties of pain assessment tools used in this setting. Our objective was to validate use of the modified Brief Pain Inventory through reanalysis of pain data from a multiple-dose, placebo-controlled, randomized trial of analgesia after coronary artery bypass graft surgery. METHODS: Four hundred sixty-two patients who underwent coronary artery bypass graft surgery via median sternotomy were administered a shortened form of the original Brief Pain Inventory that contained 3 severity and 5 interference items. Additionally, patients were presented with a single-item measure of procedure-specific pain. Daily pain and interference ratings were available from days 4 to 14 postoperatively. We performed factor analysis to evaluate the consistency with which the modified Brief Pain Inventory items loaded on 2 separate factors corresponding to the original Brief Pain Inventory's pain severity and pain interference subscales. We calculated 2 reliability measures, internal consistency and test-retest reliability, for each subscale. RESULTS: The modified Brief Pain Inventory consistently measured 2 underlying constructs, severity and interference, with Cronbach alphas of 0.85 or greater for the 2 Brief Pain Inventory scales, and test-retest stability coefficients ranging from 0.58 to 0.95 for each pair of consecutive assessment periods. The procedure-specific pain question showed substantial overlap with a general measure of pain severity, suggesting concurrent validity. DISCUSSION: The modified Brief Pain Inventory was stable and valid over the assessment period, suggesting that it can be used during the subacute postoperative period to assess postoperative pain among patients with coronary artery bypass graft surgery.

Aged↗