Biomedical subjects

T Holford

Publications and source records attributed to T Holford.

23 records · Page 2Linked to original sources

PubMed1984

The biological relationship of mouse hepatitis virus (MHV) strains and interferon: in vitro induction and sensitivities.

Five prototype strains of mouse hepatitis virus (MHV) -1, -3, -S, -A59 and -JHM were analyzed for their ability to induce interferon (IFN) in seven cell lines of rodent origin. Induction of IFN by all of the prototype MHV strains was infrequent and unpredictable, while IFN was produced consistently by five cell lines treated with known inducers. Priming and/or aging of cells did not enhance IFN induction by the MHV strains except in the case of MHV-A59 which consistently induced moderate levels of IFN on L-cells which were both primed and aged. Kinetic studies of MHV-A59-induced IFN on primed and aged L-cells demonstrated that detectable levels of IFN were not produced until 24 hours post-inoculation (p.i.). Peak levels were attained at 30 hours p.i. with no additional IFN produced through 48 hours p.i. MHV-induced IFN was similar in composition and properties to Newcastle disease virus-induced IFN. The sensitivities of the five MHV strains to eight concentrations of preformed L-cell IFN were also assessed. All strains except MHV-S fit a linear model with MHV-3, MHV-A59 and MHV-JHM having similar slopes. At most concentrations MHV-3 was less sensitive than MHV-1, -A59 or -JHM to IFN. The response curve for MHV-S was non-linear. This strain was more sensitive to the antiviral effects of the pre-formed IFN except at the highest concentrations of IFN used.

Animals↗

PubMed1982

Regional myocardial lidocaine concentration following continuous intravenous infusion early and later after myocardial infarction.

The regional concentration of lidocaine using a double constant infusion technique (250 micrograms/kg/min x 15 minutes followed by 35 micrograms/kg/mg/min x 120 minutes) was studied immediately (2 hours) in seven dogs and 24 hours (six dogs) after myocardial infarction. Tissue levels were determined by gas chromatography and related to regional myocardial blood flow as determined by the radioactive microsphere technique in multiple samples. At 2 hours after infarction a significantly higher lidocaine concentration (4.1 +/- 0.42 micrograms/g) was found in zones with greatly reduced blood flow (regional myocardial blood flow less than 0.2 ml/min per g) when compared with that (2.6 +/- 0.19 micrograms/g) in zones with normal blood flow (regional myocardial blood flow greater than 0.8 ml/min per g) (p less than 0.01). In contrast, in the 24 hour model the opposite situation was observed. Although the concentration of lidocaine in the infarct zone was substantial, a significant decline in lidocaine tissue concentration was found in the zones of lowest blood flow (regional myocardial blood flow less than 0.2 ml/min per g) when compared with that in normal zones (1.76 +/- 0.21 versus 3.38 +/- 0.21 micrograms/g, p less than 0.001). In addition, no significant differences in lidocaine concentrations were found between endocardium and epicardium in any of the groups other than those related to regional myocardial blood flow. Thus, with the double constant infusion technique, lidocaine reached normal and ischemic myocardium in concentrations equivalent to therapeutic plasma concentrations, even in lower infarct blood flow zones, with no significant differences between endocardium and epicardium. Of perhaps greater significance, the age of the ischemic insult is an important determinant of lidocaine tissue distribution in infarcted myocardium.

Animals↗

PubMed1981

Regional myocardial kinetics of lidocaine in experimental infarction: modulation by regional blood flow.

The regional myocardial concentration of lidocaine after intravenous bolus administration was studied in the setting of myocardial infarction in 27 dogs utilizing a 24 hour old infarct model. Myocardial levels of lidocaine measured by gas chromatography were related to regional myocardial blood flow measured by radioactive microspheres in the same sample. A highly significant positive linear relation was noted between relative regional myocardial blood flow and lidocaine tissue concentration in animals killed 1 and 3 minutes after the injection of lidocaine (R2 = 0.81 and 0.85, respectively). This positive linear relation was no longer evident at 5 or more minutes after injection of lidocaine. This lack of linear relation resulted from dramatic reductions in myocardial lidocaine concentration in normally perfused zones with much lesser reductions in lower flow zones. Thus the initial distribution of lidocaine after bolus injection is directly proportional to myocardial blood flow within the first 3 minutes of injection. Thereafter, the washout of lidocaine appears to be the dominant factor in myocardial distribution.

Animals↗

PubMed1979

A computer program for life table regression analysis with time dependent covariates.

This paper presents a computer program for analyzing time-dependent covariables in survival studies by the life table regression model described by Holford [3]. Basically, life table regression incorporates the elements of regression and the life table into a single model. Regression parameters are estimated by the method of maximum likelihood using the Newton-Raphson iterative procedure. The program provides two methods for testing hypotheses concerning regression coefficients, namely the standard normal deviate test and a Wald statistic based on the first and second derivatives of the log likelihood. Residual plots are provided to assess the fit of the model to the data.

Actuarial Analysis↗

PubMedDate not supplied

Menarcheal age and habitual miscarriage: evidence for an association.

Among women who habitually miscarried (two or more miscarriages) we observed a modest association for increased risk of miscarriage of first pregnancies in those with younger (especially less than or equal to 11 years) and older (greater than or equal to 16 years) menarcheal age (quadratic G2 = 3.49, P = 0.062). No associations of menarcheal age with first pregnancy miscarriage were observed when analysed by age at first pregnancy, or with pregnancy number among women with only one miscarriage. Unusually early or late menarcheal age appears to increase the risk of miscarriage of the first pregnancy but only among women who will go on to habitually miscarry.

Abortion, Habitual↗