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PubMed2005

Can the relation between tooth loss and chronic disease be explained by socio-economic status? A 24-year follow-up from the population study of women in Gothenburg, Sweden.

The objective of this study was to evaluate the association between number of missing teeth and all cause, cardiovascular, and cancer mortality as well as morbidity and to explore whether socio-economic factors mediate this association. An ongoing prospective cohort study of 1462 Swedish women included a dental survey in 1968/69 with follow-up until 1992/93. The dental examination included a panoramic radiographic survey and a questionnaire. Number of missing teeth at baseline was analysed in a Cox proportional hazards model to estimate time to mortality and morbidity. Number of missing teeth, independently of socio-economic status variables (the husband's occupational category, combined income, and education) was associated with increased all cause mortality and cardiovascular disease mortality respectively (relative risk (RR): 1.36; 95% confidence interval (95% CI): 1.18-1.58) and (RR: 1.46; 95% CI: 1.15-1.85 per 10 missing teeth), but no associations were found for cancer mortality (RR: 1.18; 95% CI: 0.91-1.52). The relation between poor oral health and future cardiovascular disease could not be explained by measures of socio-economic status in this study.

Adult↗

PubMed2006

Can dissenting findings regarding the comparative effectiveness of ICSI and IVF be explained by a learning curve?

PURPOSE: To determine whether between-trial heterogeneity in relative risk of fertilisation for intracytoplasmic sperm injection (ICSI) compared to in vitro fertilisation (IVF) can be explained by learning or by between-trial variation in patient characteristics. METHODS: Systematic review and meta-analysis of trials comparing fertilisation outcomes for ICSI and IVF (without surgical sperm retrieval). Meta-regressions to identify associations between treatment effect and trial characteristics. RESULTS: Coefficients on individually significant covariates from the meta-regressions confirm that the ICSI versus IVF treatment effect is increased when patients are "unsuited for IVF" but reduced as semen quality improves and when IVF insemination concentrations are increased. However, the relative risk of fertilisation varies inversely with publication date; contrary to the hypothesised learning effect. CONCLUSION: While it is recognised that publication date might proxy for unobserved covariates, the possibility of a learning effect in favour of ICSI is not supported by the meta-regression.

Female↗

PubMed2004

Explained variation and predictive accuracy in general parametric statistical models: the role of model misspecification.

When studying a regression model measures of explained variation are used to assess the degree to which the covariates determine the outcome of interest. Measures of predictive accuracy are used to assess the accuracy of the predictions based on the covariates and the regression model. We give a detailed and general introduction to the two measures and the estimation procedures. The framework we set up allows for a study of the effect of misspecification on the quantities estimated. We also introduce a generalization to survival analysis.

Female↗

PubMed2006

tNOX, an alternative target to COX-2 to explain the anticancer activities of non-steroidal anti-inflammatory drugs (NSAIDS).

Our work has identified a cancer-specific, cell surface and growth-related quinol oxidase with both NADH oxidase and protein disulfide-thiol interchange activities, a member of the ECTO-NOX protein family designated tNOX. We provide evidence for tNOX as an alternative drug target to COX-2 to explain the anticancer activity of COX inhibitors. Non-steroidal anti-inflammatory drugs (NSAIDS), piroxicam, aspirin, ibuprofen, naproxen and celecoxib all specifically inhibited tNOX activity of HeLa (human cervical carcinoma) and BT-20 (human mammary carcinoma) cells (IC(50) in the nanomolar range) without effect on ECTO-NOX activities of non-cancer MCF-10A mammary epithelial cells. With cancer cells, rofecoxib was less effective and two NSAIDS selective for COX-1 were without effect in inhibiting NOX activity. The IC(50) for inhibition of tNOX activity of HeLa cells and the IC(50) for inhibition of growth of HeLa cells in culture were closely correlated. The findings provide evidence for a new drug target to account for anticancer effects of NSAIDS that occur independent of COX-2.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2005

The appearance of long-latency responses to a conditioned signal in the cortex is explained by strengthening of collateral connections between pyramidal neurons.

Experimental analysis and computer simulation of the neurophysiological processes underlying the "stable and local electrophysiological expression of conditioned reflexes" in the cerebral cortex, a phenomenon discovered in Asratyan's laboratory in the 1960s, showed that the long-latency components of cortical evoked potentials to a conditioned signal correspond to the late phases of the responses of motor cortex neurons, which are analogous to and probably generated by the same mechanism as long-latency epileptiform reactions of neurons in the epileptogenic cortex. Late long-latency components are generated via activation of NMDA receptors in the collateral connections between pyramidal neurons. The delay in the generation of responses depends on the initial activation of GABA(A) receptors and the slow kinetics of the current through NMDA channels. The appearance of late components as a result of training is explained by increases in the efficiency of collateral excitatory connections between pyramidal neurons.

Animals↗

PubMed2006

Female predominance in meningiomas can not be explained by differences in progesterone, estrogen, or androgen receptor expression.

The female predominance in meningioma incidence and association between meningioma and breast cancer suggest that growth of meningiomas is hormone-dependent. There are several discrepancies in literature about the proliferative effect of sex hormones on meningiomas. This study aims to evaluate the hormone receptor status of meningiomas and assess its relation to age, sex, histological grade, recurrence, and proliferation activity. The material was based on consecutive patients operated for meningioma at Tampere University Hospital in 1989-1999. The occurrence of progesterone, estrogen and androgen receptor in patients with primary and recurrent meningiomas was studied immunohistochemically by using specific monoclonal antibodies. Hormonal status was determined in 510 tumor samples. 443 samples were from primary meningiomas and 67 from recurrent tumors. Of the samples, 455 were benign (WHO grade I), 49 atypical (grade II), and 6 malignant (grade III). Of the primary tumor samples, 88% were progesterone receptor positive, 40% were positive for estrogen and 39% for androgen receptors. Grade I meningiomas had significantly higher incidence for estrogen and androgen receptors than higher grade meningiomas. Estrogen positive tumor samples had significantly higher proliferation index than estrogen negative samples. No difference in expression of sex hormone receptors was observed by sexes or age group. Estrogen and androgen receptors may have more influence on the pathogenesis of meningiomas than earlier thought. The higher incidence of meningiomas in women can not be explained by differences of sex hormone receptor expression.

Age Factors↗

PubMed1989

Models explaining motor vehicle death rates in the United States.

This paper is a selective survey of models explaining motor vehicle death rates in the United States. First, it reviews Peltzman's 1975 study of the effect of automobile safety regulation and critiques of the study. Then it summarizes several subsequent statistical studies of highway fatalities. The surveyed studies are typically regression analyses of the impact of various factors on motor vehicle deaths. They are categorized in this paper according to which of three types of data they utilized: time-series; cross-sectional; or pooled time-series, cross-sectional. This paper notes what can be inferred collectively from the surveyed studies regarding the impacts of various factors on highway fatalities. It also discusses certain shortcomings of the studies in general along with possible remedies, and makes recommendations regarding future research. Tabular summaries of the statistical studies surveyed in this paper are included in the Appendix.

Accidents, Traffic↗

PubMed1989

Is a decrease in plasma oncotic pressure enough to explain the edema of pregnancy?

The balance of fluid across capillaries is given by the Starling equation. Because the plasma protein concentration (one of its components) is decreased in pregnancy, we decided to explore the question as to whether hypoproteinemia with intact protein mass (produced by blood volume expansion) or hypoproteinemia with decreased total protein mass (produced by removal of circulating proteins) alters the oncotic pressure differences across capillaries. We calculated the oncotic pressure difference obtained in seven nonpregnant ewes during periods of normoproteinemia and hypoproteinemia; the influence of fluid infusion under both conditions was also observed. There was an increase in the oncotic pressure difference across the capillary wall during hypoproteinemia produced by a decrease in the total protein mass (p less than 0.01); however, the response to hypoproteinemia produced by fluid infusion was similar (p greater than 0.1). The venous pressure (used as an index of interstitial fluid pressure changes) did not differ in either hypoproteinemia or fluid infusion. Capillary permeability was decreased during hypoproteinemia, as evidenced by a higher lymph/protein ratio of labeled albumin during the control period (p less than 0.05). In conclusion, during a state of decreased plasma protein concentration similar to that of pregnancy, the difference in the oncotic pressure and hydrostatic pressure forces acting to prevent transfer of fluid to the interstitium is increased. Therefore other factors that influence fluid transfer across the capillaries must be investigated to explain the edema of pregnancy.

Animals↗

PubMed1984

Observed differences in postoperative lymphocyte transformation are explained by patient and population variations.

In the present study, the kinetics of the lymphocyte response to phytohemagglutinin were examined by harvesting lymphocytes at 24 hour intervals in four nonoperated control subjects, preoperatively and postoperatively in six men who underwent herniorrhaphy, and in four people who had colectomy for adenocarcinoma. Nonorthogonal analysis after logarithmic transformation and adjustment for individual and population variations showed no differences in preoperative and postoperative transformation. No age effects were seen. The previous evidence that surgery inhibits transformation to phytohemagglutinin was explained by wide kinetic variations in both patient and control populations.

Adenocarcinoma↗

PubMed1995

Genetic heterogeneity may in part explain sex differences in the familial risk for schizophrenia.

The purpose of this study was to attempt, in part, to explain significant sex differences in the familial risk (FMR) for schizophrenia found in previous studies. We hypothesized that, like probands, relatives of male vs. female probands may express different forms or subsyndromal symptoms of schizophrenia, i.e., differential expression of flat affect. Studied were 332 schizophrenic probands defined by Diagnostic and Statistical Manual of Mental Disorders, 3rd ed. (DSM-III), criteria and 725 first-degree relatives from well-known retrospective cohort family studies. Results showed that relatives of male probands were at significantly higher risk for expressing flat affect than relatives of female probands, which did not hold for relatives of normal controls. Logistic regression was used to show that when flat affect was incorporated into the definition of affected among relatives, sex differences in FMR disappeared.

Adult↗

PubMed1984

Suppression of C-fibre discharges upon repeated heat stimulation may explain characteristics of concomitant pain sensations.

Nociceptors with unmyelinated axons were recorded from the superficial radial nerves of 7 volunteers. A sequence of uniform radiant heat stimuli of 18 s duration, starting from an individually adjusted adapting temperature were used to raise the skin surface temperature by 6 degrees C to a painful level (41-43 degrees C). These stimuli followed each other at 3 different interstimulus intervals of 35 s, 70 s and 105 s, occurring in a random order. The subjects were asked to track the time course of the stimulus-evoked sensation by manipulating the length of a light bar. Adaptation and stimulus temperatures were chosen to induce sensations of heat and/or pain. All nociceptors studied responded to these stimuli with a phasic response of 3-5 s duration, often followed by a low frequency tonic discharge, lasting as long as the stimulus. No discharges were seen in interstimulus periods. Discharge rates during the phasic responses were linearly related to interval duration, whereas tonic discharges were not influenced by the preceding interval. In parallel readings of pain responses were lower up to the 10th second of the stimulus after short rather than after long intervals. These results indicate that the suppression of C-fibre nociceptor discharges during repetitive stimulation may explain concomitant reductions in the magnitude of human pain sensations.

Adult↗

PubMed1995

The molecular switch hypothesis fails to explain the inconsistent effects of the metabotropic glutamate receptor antagonist MCPG on long-term potentiation.

In the CA1 region of the hippocampus, the induction of long-term potentiation (LTP) appears to be controlled by a switch-like biochemical process that is persistently activated following metabotropic glutamate receptor (mGLUR) activation. However, the mGLUR antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) does not consistently block the induction of LTP, perhaps because the experimental conditions used by some investigators inadvertently activate this 'molecular switch', thereby fulfilling the requirement for mGLUR activation and rendering LTP insensitive to the effects of mGLUR antagonists. In mouse hippocampal slices we observed that MCPG does not block LTP induced by high-frequency stimulation, Moreover, stimulation protocols designed to deactivate an inadvertently activated molecular switch had no effect on the inability of MCPG to block LTP. MCPG (through a switch-independent mechanism) did inhibit the induction of LTP by a weak induction protocol. Our results thus suggest that MCPT-sensitive mGLURs are not required for the induction of LTP and that a mLGUR-activated 'molecular switch' does not explain the inconsistent effects of MCPG on LTP. Instead, MCPG-sensitive mGLURs may have a modulatory role in the induction of LTP that is most evident when LTP is induced by near threshold patterns of synaptic stimulation.

Animals↗

PubMedDate not supplied

Explaining diagnostic complexity in an intake setting.

A one patient-one illness paradigm is implicit in the history and theory of psychiatry, and in basic research. Yet, in clinical practice and treatment populations in general, more than one diagnosis per patient is frequently encountered. How clinicians formulate comorbidity by means of DSM-III has rarely been investigated. In this study, the ideas of clinical condition and that of its diagnostic complexity are used to analyze descriptive features of a large number of patients seen in an intake setting. Axis I of DSM-III is used to measure diagnostic complexity. Complexity is analyzed in relation to demographic variables, to ratings entered in the remaining axes of DSM-III formulations, to symptom levels of patients, and to decisions involving disposition. Results indicate that analysis of diagnostic complexity by means of DSM-III yields a definable structure and that it can be related meaningfully to clinical factors. The idea of information uncertainty in diagnosis, i.e., the opacity versus transparency of a clinical condition, is also used to explain results. The ideas introduced and studied are shown to have value for social psychiatric research.

Adaptation, Psychological↗

PubMed1983

Competitive inhibition of nicking--closing enzymes may explain some biological effects of DNA intercalators.

Intercalating agents cause varied and multiple biological effects. These include the inhibition of RNA and DNA synthesis, frameshift mutations and protein-associated DNA breaks. However, some non-intercalating analogs of intercalating compounds behave similarly. The model of DNA intercalation does not adequately explain all these biological effects. It is suggested here that intercalators and similar compounds may competitively inhibit the closing reaction of some nicking--closing enzymes. Hypothetical mechanisms built on this suggestion are presented for the formation of protein associated DNA breaks, frameshift mutation, inhibition of macromolecular synthesis, and recombination.

Animals↗

PubMed1991

Oxidation/reduction explains heterogeneity of pancreatic somatostatin.

Somatostatin 14 (SS 14) has been isolated from pancreatic extracts, but open gel filtration immunoreactive SS often elutes in two peaks. We isolated both peaks, but upon sequence analysis only authentic SS 14 could be identified. By further gel filtration experiments it turned out that both synthetic and extractable SS appeared homogeneous at neutral pH 7.5, but showed an additional, earlier peak in acetic acid. After addition of mercaptoethanol, all of the SS eluted at this earlier position regardless of the pH. We conclude that partial reduction/oxidation of SS explains the heterogeneity.

Amino Acid Sequence↗

PubMed1993

A structural model for the glutamate-specific endopeptidase from Streptomyces griseus that explains substrate specificity.

We present a model for the three-dimensional structure of the glutamate-specific endopeptidase from Streptomyces griseus based on the crystal structures of other bacterial proteases of the trypsin family. For the first time a structural model is described which attempts to explain the basis of P1 glutamate specificity in serine proteases. Several important changes to the S1 pocket with respect to other members of the family of different specificity are described. Of particular interest is the presence of a histidine at position 213 and the substitution of Arg-138 by lysine. Other biochemical evidence concerning substrate preferences can be rationalized on the basis of the model.

Amino Acid Sequence↗

PubMed1995

Do physical and chemical working conditions explain the association of social class with ischaemic heart disease?

The aim of this study was to examine whether physical and chemical working conditions explain the association of social class with ischaemic heart disease (IHD). We investigated the issue in a cohort of 2974 males aged 53-75 years (mean 63) free from overt cardiovascular disease. Potential confounders included were: alcohol consumption, physical activity, tobacco smoking, serum cotinine, serum lipids, serum selenium, body mass index, blood pressure, hypertension, social class, and retirement status. During the follow-up period (1985-1986 to 31 December 1991), 184 men (6.2%) had a first IHD event; 44 events were fatal. Compared to higher social classes (classes I, II and III), lower classes (classes IV and V) had a significantly increased risk of IHD (P < 0.05); the age-adjusted relative risk (RR) with 95% confidence limits was 1.44 (1.06-1.95), P = 0.02. Mean who had been occupationally long-term exposed (> or = 5 years) to either soldering fumes or organic solvents had a significantly higher risk of IHD than unexposed: RRs were 2.1 and 1.7, respectively. After adjustment for all the above potential confounders and including also these two occupational factors, the RR of low social classes was reduced to a non-significant 1.24 (0.87-1.76), P = 0.24, i.e. by 45%. Adjusting for non-occupational factors only reduced the RR from 1.44 to 1.38 (1.0-1.90), P = 0.05, i.e. by about 14%. Assuming that the association of soldering fumes and organic solvents with risk of IHD was causal, it was estimated that 16% of IHD cases in low social class could be ascribed to these exposures.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Three-dimensional tissue deformation in subcutaneous tissues overlying bony prominences may help to explain external load transfer to the interstitium.

Anesthetized, carefully positioned, female, weanling, white-haired pigs were used to test the hypothesis that (1) interface pressure, the pressure between the skin and an external load, can be used to predict the interstitial fluid pressure over the wings of ilia and the last dorsal spinous process and (2) three-dimensional tissue deformation of the interstitium under the load could partially explain how the external load is transferred at that site. When a 4 or 8 kg load was distributed over the hips of the pigs, the interface pressures over the ilia were approximately 145 and 207 cm H2O, respectively. Approximately 28% of this pressure was transferred to the tissue, resulting in an increase in interstitial fluid pressure of approximately 39 cm H2O for the 4 kg load and 60 cm H2O for the 8 kg load. However, over the spinous process, about 42-43% of the load was transferred to the interstitium. Subcutaneous tissue marker movement occurred along the gamma and theta spherical coordinate but no significant tissue marker movement along the phi coordinate. The latter indicates no significant twisting of the tissue while the former demonstrates three-dimensional shearing. There were also indications of tissue creep since the markers continued to move with constant loading.

Animals↗