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Biomedical subjects

M Goddard

Publications and source records attributed to M Goddard.

At least 55 records · Page 3Linked to original sources
PubMed1995

Comparison of the up-and-down, conventional LD50, and fixed-dose acute toxicity procedures.

The up-and-down procedure (UDP), fixed-dose procedure (FDP) and conventional LD50 tests were compared to determine their consistency in chemical hazard classification for acute oral toxicity according to the European Economic Community (EEC) system. There was consistent classification for 23 out of 25 cases between the UDP and the conventional LD50 results, in 16 out of 20 cases between the FDP and the conventional LD50, and in seven out of 10 cases between the UDP and the FDP. The UDP needed only between six and 10 animals of one sex (fewer than either the LD50 or the FDP). Available literature indicates that the sexes are usually similar in their acute toxicity responses and that of females are often more sensitive than males when acute toxicity differences do exist, thus obviating the need for both sexes to be tested in most cases. Unlike the FDP, the UDP also estimates an LD50, thus providing data directly applicable to all current hazard classification systems based on acute oral toxicity.

Animals↗
PubMed1994

Functional recovery in hemiparkinsonian primates transplanted with polymer-encapsulated PC12 cells.

Cross-species neural grafting of cell lines immunoisolated by a permselective polymer membrane represents a promising source of neuroactive molecules for the treatment of neurodegenerative diseases. Utilization of a cell line of xenogeneic origin is advantageous since the transplanted cells will be rejected by the host immune system in case of breakage of the immunoisolating envelope. Polymer-encapsulated PC12 cells, a dopaminergic cell line derived from a rat pheochromocytoma, were transplanted in five Macaca fascicularis monkeys which had been previously rendered hemiparkinsonian by a unilateral carotid injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Well-preserved, tyrosine hydroxylase positive encapsulated PC12 cells were observed in the lesioned striatum for up to 5 months after implantation. Four out of five monkeys which received polymer-encapsulated PC12 cells showed significant behavioral improvement, whereas three monkeys implanted with either encapsulated bovine chromaffin cells or empty polymer envelopes showed no amelioration.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

A hypertonic infusion in the treatment of experimental shock in calves and clinical shock in dogs and cats.

A novel composite hypertonic solution for intravenous use was tested in two experimental models, one of endotoxic shock and one of shock linked with dehydration, both in anaesthetised calves. Endotoxic shock was induced with Escherichia coli lipopolysaccharide and was characterised by a low cardiac output, hypoxaemia, acidosis and anuria. Treatment with a small volume of the solution increased cardiac output, improved oxygen carriage, corrected acidosis and stimulated renal function. Experimental dehydration in calves was induced by intraperitoneal mannitol and frusemide diuresis, and was characterised by reduced circulating plasma volume, acidosis and poor peripheral perfusion. Treatment with the new solution corrected the acidosis and stimulated peripheral circulation significantly better than treatment with hypertonic or isotonic saline alone, and also expanded the calves' plasma volume. The new solution was also compared with conventional fluid therapy in clinical small animal practice. Twenty cats and dogs with clinical shock were treated with either small volumes of the hypertonic solution or large volumes of isotonic fluids. The animals treated with small volumes of the hypertonic solution responded better than the animals treated with large volumes of isotonic fluid.

Animals↗
PubMed1993

Economic evaluation and quality of life assessments in cancer clinical trials: the CHART Trial.

Arguments are being made more frequently to incorporate economic evaluations and quality of life assessments into clinical trials. Using a randomised, multicentre, phase 3 cancer clinical trial as an example, this paper outlines the importance of including such assessments; the practical considerations associated with the design of such trials; the methods for collecting such data; and, how such data can be used. Finally, it is emphasised that the anticipated benefits of collecting data relating to resource use and quality of life should outweigh the associated costs to research funding organisations.

Clinical Trials, Phase III as Topic↗
PubMed1993

Very small-diameter polyurethane vascular prostheses with rapid endothelialization for coronary artery bypass grafting.

Two types of spongy polyurethane-polydimethylsiloxane blend (Cardiothane 51, Kontron Instruments, Inc., Everett, Mass.) vascular grafts with an internal diameter of 1.5 mm were fabricated by a spray, phase-inversion technique. Low-porosity grafts with hydraulic permeability of 2.7 +/- 0.4 ml/min per square centimeter and medium-porosity grafts with hydraulic permeability of 39 +/- 8 ml/min per square centimeter displayed good handling properties and suturability. Twelve straight low-porosity grafts, 17 straight medium-porosity grafts (1.5 to 2.0 cm in length), and one loop medium-porosity graft (10 cm in length) were implanted by the same surgeon end to end in the infrarenal aorta of 30 male Sprague-Dawley rats. Three months after implantation, patency was 8% for low-porosity grafts (1/12) and 76% for straight medium-porosity grafts (13/17). The loop medium-porosity graft was also patent. The sole patent low-porosity graft showed neointimal hyperplasia and incomplete endothelialization. All but one of the patent straight medium-porosity grafts showed a glistening and transparent neointima with complete endothelialization and no anastomotic hyperplasia. The loop medium-porosity graft displayed endothelialization from each anastomosis and in many islands in the middle portion of the graft, totalling 47% of the luminal surface by morphometric analysis. Thick mural thrombus, anastomotic hyperplasia, or aneurysm formation were not observed in any patent medium-porosity graft. These data indicate that in the rat aortic replacement model it is possible to achieve patency and a high degree of endothelialization in very small-diameter prostheses of appropriate porosity.

Animals↗
PubMed1992

Modification of tumor promotion in the mouse skin by exposure to an alternating magnetic field.

Some epidemiological studies have suggested that exposure to an alternating magnetic field may increase the incidence of some cancers. Our earlier study of carcinogenesis in mouse skin, indicated that exposure to a magnetic field (MF) alone did not promote the growth of tumors. In the present experiment, the ability of a MF to act as a tumor copromoter was investigated. The dorsal skins of female SENCAR mice (6-7-weeks-old) were treated with 10 nmol of 7,12-dimethylbenzanthracene (DMBA) to initiate the carcinogenic process and then tumor development was promoted, for 23 weeks, by weekly applications of 4.9 nmol (0.3 microgram) of 12-0-tetradecanoylphorbal-13-acetate (TPA). One group of 48 mice were exposed to a 60-Hz magnetic field of 2 mT (20 Gauss) for 6 h/day 5 days/week, while a similar group (48 mice) were sham exposed. After week 12, the percentage of mice with tumors and the mean number of tumors per mouse, were higher for the group exposed to MF. At week 18, for example, where the differences between field and sham groups were statistically significant, the percentage of mice with tumors were, respectively, 25% and 8% (P less than 0.05, Fisher exact) and, the mean yield of tumors 1.9 +/- 0.69 and 0.65 +/- 0.46 (mean +/- S.E.M.) (P less than 0.05, Wilcoxon). At week 23 these differences were no longer statistically significant.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

Atrial natriuretic peptide in newborn piglets with a patent ductus arteriosus.

Atrial natriuretic peptide (ANP) is a hormone involved in fluid and blood pressure homeostasis. We studied the effects of left-to-right shunting through a patent ductus arteriosus on blood pressure changes and plasma ANP concentrations in newborn piglets. In five experimental piglets, the ductus arteriosus was bathed with PGE1 and infiltrated with formalin to maintain its patency. In four age-matched control piglets, the ductus arteriosus was ligated. Plasma ANP concentrations and blood pressure determinations were obtained prior to (base-line) and 25 +/- 1 h (day 1), and 48 +/- 1 h (day 2) after surgery. Radionuclide-microsphere determinations of left-to-right patent ductus arteriosus shunts were performed on days 1 and 2 in the 5 piglets with a patent ductus arteriosus. Plasma ANP concentrations were significantly elevated in the left atrium on day 1 and the right atrium on day 2 in the PDA piglets. No correlation was demonstrated between plasma ANP concentrations and right or left atrial pressures. We conclude that left and right plasma atrial ANP concentrations are significantly elevated in newborn piglets with left-to-right patent ductus arteriosus shunts.

Animals↗
PubMed1991

Comparison of dorsal and ventral spinal root regeneration through semipermeable guidance channels.

Semipermeable guidance channels have been shown to support nerve regeneration in the peripheral nervous system (PNS) possibly through interactions with the wound healing environment. This study quantitatively assesses the ability of such channels to support regeneration in the PNS segment of the spinal roots across a 4 mm gap and compares the resultant dorsal and ventral root regeneration. Acrylic copolymer guidance channels with a molecular weight (Mw) cutoff of 50,000 Da were used in a transected rat spinal root model. Cohorts of 23 animals (11 ventral, 12 dorsal) were examined at four weeks; 6 animals (3 ventral, 3 dorsal) at ten weeks; and 10 animals (5 ventral, 5 dorsal) at twenty-four weeks post-implantation. Both the dorsal and ventral roots were able to regenerate across the gap within the semipermeable channel. At all time periods, the regenerated dorsal roots contained fewer myelinated axons than found in the contralateral control root and consisted of an abundance of collagenous tissue. In contrast, by ten weeks the regenerated ventral roots contained twice the contralateral control number of myelinated axons and were composed predominantly of large, myelinated axons. At twenty-four weeks the number of unmyelinated axons was also quantified, with the regenerated dorsal root containing only one-fifth of the control number and the regenerated ventral root containing more than four times the control. Due to the proximity of the dorsal root lesion to the axonal cell bodies, the dorsal root ganglion (DRG) neuronal cell loss was investigated at four weeks post-implantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Cancer promotion in a mouse-skin model by a 60-Hz magnetic field: II. Tumor development and immune response.

This paper describes preliminary findings on the influence of 60-Hz (2-mT) magnetic fields on tumor promotion and co-promotion in the skins of mice. The effect of magnetic fields on natural killer (NK) cell activity in spleen and blood was also examined. Groups of 32 juvenile female mice were exposed to the magnetic field as described in part I. The dorsal skin of all animals was treated with a subthreshold dose of the carcinogen 7,12-dimethyl-benz(a)anthracene (DMBA). One week after the treatment, two groups were sham exposed (group A) or field exposed at 2 mT (group B) 6 h/day for 21 weeks, to test whether the field would act as a tumor promoter. No tumors developed in these two groups of mice. To test whether the magnetic field would modify tumor development by directly affecting tumor growth or by suppressing immune surveillance, two additional groups of mice were treated weekly with the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) and then either sham exposed (group C) or field exposed (group D). The time to appearance of tumors was shorter (but not statistically so) in the group exposed to magnetic fields and TPA. Some differences in NK cell activity and spleen size were observed between the sham- and field-exposed groups.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1991

Effect of solute on the nucleation and propagation of ice.

Using the emulsion technique, we have studied nucleation of ice in aqueous solutions containing silver iodide or Pseudomonas syringae. Using a Differential Scanning Calorimeter (DSC), we determined characteristic temperatures of nucleation, and also rates of nucleation at selected temperatures. The freezing point depression induced by added solute is linearly related to the lowering of both homogeneous and heterogeneous nucleation temperature. Nucleation kinetics depend on a fifth power function of the temperature. Solute is found to affect the parameters of this relationship in different ways, dependent upon the nature of the catalytic site for ice nucleation. We have also studied the effect of composition on the linear propagation velocity (LPV) of ice in undercooled solutions contained in a U-tube. We have determined velocities in a range of concentrations of sugar solution at the same undercooling, and also as a function of undercooling. The role of added polymer has also been investigated. It is affected by the sugar concentration.

Calorimetry, Differential Scanning↗
PubMed1991

Palliative radiotherapy--counting the costs of changing practice.

"Working for Patients', the government's review of the National Health Service (NHS) advocates reforms which have led inevitably to pressure for medical specialities to review both the outcomes of their services and the resources used in achieving these outcomes. This paper considers these issues in the context of provision of palliative radiotherapy for patients with incurable cancers and presents the results of a study which evaluated the costs of radiotherapy. In addition to producing some of the first detailed cost estimates for the delivery of radiotherapy, this exercise highlighted the methodological and practical difficulties of undertaking such studies. As increasing pressure to evaluate cancer therapy is a prominent feature of a 'post-NHS Review' world, lessons learnt from this study may also be applicable to the audit of other cancer therapies. Efficient audit practices will, of course, have to evaluate the benefits (in terms of enhancements to length and quality of life) as well as the costs of cancer therapies.

Capital Expenditures↗
PubMed1991

Economic evaluation of trends in cancer therapy. Marginal or average costs?

Evaluating the use of resources as well as outcomes in cancer therapy is increasingly becoming recognized by both clinicians and others as a legitimate and indeed even desirable activity. While this trend is to be welcomed if it facilitates the efficient use of resources for cancer care, there are dangers in applying estimates of unit costs, in particular average costs to the evaluation of trends in practice in cancer therapies. This article examines the use of appropriate measures of average and marginal cost in the economic evaluation of developments in cancer therapy, taking illustrations from radiotherapy and chemotherapy.

Antineoplastic Agents↗