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Biomedical subjects

D M Wood

Publications and source records attributed to D M Wood.

At least 19 recordsLinked to original sources
PubMed1999

Aspirin usage in a large teaching hospital diabetes clinic setting.

AIM: To document aspirin usage and the prevalence of large and small vessel complications in patients with diabetes mellitus (DM) attending the outpatient diabetes clinics of a large public hospital. METHODS: All patients attending diabetes outpatient clinics at The Royal Melbourne Hospital in Melbourne, Australia were surveyed over a 3-month period. RESULTS: Complete data were available on 629 of 632 (296 male) patients surveyed. Of the 29.3% of patients who were suffering from one or more macrovascular complication (ischaemic heart disease, cerebrovascular disease or peripheral vascular disease), 63% were currently on aspirin treatment. Of those not on aspirin, 65% had no contra-indication to aspirin treatment and a further 19% had only a relative contra-indication of either aspirin or warfarin treatment recorded. CONCLUSIONS: The published recommendations for the use of aspirin in patients with macrovascular disease were generally being followed in this clinic-based population. However, a significant proportion of patients without a contra-indication to treatment were still not receiving aspirin. The lack of clear evidence-based guidelines for aspirin use may be a factor in its under-prescription. This survey suggests clear evidence-based guidelines should be established and disseminated.

Adult↗
PubMed1996

Variability in the plasma protein binding of velnacrine (1-hydroxy tacrine hydrochloride). A potential agent for Alzheimer's disease.

OBJECTIVES: To quantify the protein binding of velnacrine in healthy individuals and investigate potential sources of variability. SETTING: Medical School Unit, Southmead Hospital, Bristol. SUBJECTS: Plasma samples were obtained from the following groups: a) 11 healthy volunteers aged 18 to 30 years; b) 10 healthy volunteers aged 73 to 87 years; c) 10 patients aged 65 to 85 years hospitalised for a variety of acute illnesses. METHODS: Aliquots of plasma from the above subjects were incubated with various concentrations of velnacrine, in the presence and absence of tacrine hydrochloride. Standard solutions of human serum albumin and alpha 1 acid glycoprotein were incubated with velnacrine. The degree of protein binding was determined using the Amicon centrifree micropartition system. RESULTS: 1) Over the range of concentrations from 10 to 320 ng.ml-1, there was a decrease in protein binding from 59.1 to 46.7%. 2) At 40 ng.ml-1 the plasma protein binding of velnacrine was 54.8% in the group a subjects, 51.9% in the group b subjects and 53.0% in the group c subjects (NS). 3) The mean total plasma protein concentration was significantly lower in the samples from elderly subjects. The mean albumin and alpha 1 acid glycoprotein concentrations were lower and higher respectively in patients with acute disease. 4) Velnacrine was shown to bind to both albumin and alpha 1-acid glycoprotein, but together they did not account for total binding. 5) The binding of velnacrine was significantly decreased from 59.3 to 43.9% in the presence of a therapeutic concentration (25 ng.ml-1) of THA. There was no evidence that velnacrine displaced THA. CONCLUSION: Protein binding can be discounted as a major source of variation in the relationship between drug concentration and effect.

Acute Disease↗
PubMed1996

Lesion volume, injury severity, and thalamic integrity following head injury.

Magnetic resonance scans of 63 TBI patients were analyzed to examine the relationship between injury severity, lesion volume (nonthalamic cortical/subcortical lesions), ventricle-to-brain ratio (VBR), and thalamic volume. For comparison, 33 normal control subjects were used. Patients with visible nonthalamic structural lesions showed significantly smaller thalamic volumes than patients without visible lesions or control subjects. Results also indicated that patients with visible lesions had significantly more severe injuries than patients without lesions. Patients with moderate-severe injuries had significantly smaller thalamic volumes and greater VBRs than patients with mild-moderate injuries. Although several variables related to thalamic volume, the presence of nonthalamic lesions was sufficient to result in smaller thalamic volume. Decreased thalamic volume following head injury suggests that subcortical brain structures may be susceptible to transneuronal degeneration following cortical lesions, and that this can be detected by in vivo MR-based volumetric analysis.

Adult↗
PubMed1996

Lesion volume, injury severity, and thalamic integrity following head injury.

Magnetic resonance (MR) scans of 63 traumatic brain injury (TBI) patients were analyzed to examine the relationship between injury severity, lesion volume (nonthalamic cortical/subcortical lesions), ventricle-to-brain ratio (VBR), and thalamic volume. For comparison, 33 normal control subjects were used. Patients with visible nonthalamic structural lesions showed significantly smaller thalamic volumes than patients without visible lesions or control subjects. Results also indicated that patients with visible lesions had significantly more severe injuries than patients without lesions. Patients with moderate-severe injuries had significantly smaller thalamic volumes and greater VBRs than patients with mild-moderate injuries. Although several variables related to thalamic volume, the presence of nonthalamic lesions was sufficient to result in smaller thalamic volume. Decreased thalamic volume following head injury suggests that subcortical brain structures may be susceptible to transneuronal degeneration following cortical lesions, and that this can be detected by in vivo MR-based volumetric analysis.

Adult↗
PubMed1995

Diencephalic changes in traumatic brain injury: relationship to sensory perceptual function.

Magnetic resonance (MR) imaging scans of 33 traumatically brain-injured (TBI) patients were compared quantitatively to MR scans of controls matched for age and gender. Quantitative estimates of thalamic, internal capsule, and third ventricle morphology were obtained in each TBI patient. Comparisons were made to normal control subjects and revealed significant reduction in thalamic volume with corresponding increase in third ventricle. Measurements of internal capsule reflected nonsignificant changes. Significant correlations were observed between sensory-perceptual functioning, as measured by the Reitan-Kløve Sensory-Perceptual Exam, and thalamic volume in TBI patients. A decrease in thalamic volume was associated with an increase in sensory-perceptual errors.

Adolescent↗
PubMed1995

An evaluation of nitinol and stainless steel files used by dental students during a laboratory proficiency exam.

Eighty-one dental students instrumented two curved canals in acrylic blocks with the use of stainless steel files in one block and nitinol files in the other. Overlay tracings were made of photographs taken before and after instrumentation of the acrylic blocks and differences between the tracings were measured along the canal walls. The canals instrumented with nitinol files were shaped better than those instrumented with stainless steel files; working length was maintained more often without ledging the canal walls and with less zipping of the apical foramen.

Alloys↗
PubMed1994

New techniques for rearing black flies from pupae (Diptera: Simuliidae).

Simple techniques are described for collecting black fly pupae from streams using plastic strips and for rearing large numbers of adult black flies in inexpensive enclosures made of chicken wire and cloth mesh netting, and 2 methods are described for rearing adult black flies individually from pupae. The first method of rearing individual black flies uses 1.5-ml microcentrifuge tubules and the second uses easy-to-construct rearing chambers that provide moisture for the developing pupa and water for the adult to imbibe. Instructions for assembly are provided. Specimens obtained using these rearing chambers are of museum quality.

Animals↗
PubMed1992

Effects of oxazolidines derived from (-) ephedrine in the rat.

1. Five oxazolidines were synthesized by reaction of (-) ephedrine with aliphatic aldehydes. The aldehydes used were formaldehyde, propionaldehyde, butyraldehyde, isobutyraldehyde and trimethylacetaldehye. 2. These five oxazolidines were tested in rats for ephedrine-like pharmacological activity using the hyperthermia and anorexia models. 3. All five oxazolidines caused significant elevation of body temperature in the hyperthermia model. The oxazolidine synthesized from (-) ephedrine and butyraldehyde caused greatest hyperthermia. 4. Four oxazolidines caused significant anorectic responses. The oxazolidine synthesized from (-) ephedrine and isobutyraldehyde caused greatest anorexia. 5. A possible tolerance to the anorectic effects of some of the compounds was observed.

Animals↗
PubMed1992

Reactivity of monoclonal antibody E5 with endotoxin. II. Binding to short- and long-chain smooth lipopolysaccharides.

The murine monoclonal IgM antibody E5 has been shown to significantly reduce the mortality and morbidity of patients with Gram-negative sepsis in a multicenter randomized placebo-controlled clinical trial. The in vitro binding characteristics of monoclonal antibody (mAb) E5 were studied using highly purified smooth lipopolysaccharide (LPS) isolated from a variety of clinically relevant, wild-type Gram-negative bacteria. Using a sensitive antibody-capture assay which involves immobilized mAb E5 and a chromogenic Limulus amebocyte lysate (LAL) LPS-detection system, mAb E5 was shown to bind to all 15 smooth LPS preparations tested, including LPS isolated from Escherichia, Klebsiella, Proteus, Pseudomonas, Salmonella, Serratia and Yersinia species. When LPS was fractionated according to size by size-exclusion chromatography, mAb E5 was shown to bind to smooth LPS molecules that have long as well as short O-polysaccharide chains. These results confirm and extend those reported previously and demonstrate that the anti-lipid A mAb E5 binds specifically to a diverse spectrum of smooth LPS isolated from wild-type Gram-negative bacteria.

Animals↗
PubMed1992

Reactivity of monoclonal antibody E5 with endotoxin. I. Binding to lipid A and rough lipopolysaccharides.

The murine IgM monoclonal antibody (mAb) E5 was produced by a hybridoma derived from spleen cells of a mouse immunized with the J5 rough mutant of Escherichia coli O111:B4. In a multicenter randomized placebo-controlled clinical trial, E5 has been shown to reduce significantly the mortality and morbidity of patients with Gram-negative sepsis. The characteristics of E5 binding to endotoxin were studied in vitro. We report here the results of binding to an extensive panel of rough lipopolysaccharide (LPS) and lipid A preparations. Using standard immunologic techniques, including enzyme-linked immunosorbent assay (ELISA) and radioimmunoassay (RIA), as well as an antibody capture assay using immobilized antibody and a chromogenic Limulus amebocyte lysate (LAL) detection system, E5 was shown to bind to all rough LPS (chemotypes Ra through Re from Salmonella minnesota and E. coli J5) and lipid A preparations tested. E5 displayed a Kd for Ra LPS of approximately 6.5 nM. These results confirm and extend those reported previously and provide evidence that E5 binds specifically to lipid A and to the lipid A moiety of rough LPS.

Animals↗
PubMed1990

Hyperthermic and anorectic effects of oxazolidines derived from L-ephedrine in rats.

Oxazolidines synthesized from (-) ephedrine have been proposed as potential pro-drugs, but no pharmacological data on these compounds has been yet reported. In this study, four such compounds are tested in rats for ephedrine-like activity using the hyperthermia and anorexia models. The compounds were synthesized by reaction of (-) ephedrine with salicylaldehyde, acetone, cyclohexanone, and benzaldehyde, respectively. The results showed that all of the compounds decreased food intake significantly, but only the acetone and the salicylaldehyde derivatives caused a significant elevation of body temperature. All of the compounds were less effective than (-) ephedrine in the anorexia model. The acetone and salicylaldehyde derivatives showed similar potency to (-) ephedrine in the hyperthermia model.

Animals↗
PubMed1989

Mediation in the nucleus accumbens of the discriminative stimulus produced by cocaine.

Rats were trained to detect an intraperitoneal (IP) administration of cocaine, 10.0 mg/kg, using a two-lever choice discrimination procedure in which food reinforcement was only delivered following 10 responses on the correct lever (FR10): one lever was correct after cocaine injection, and the other lever was correct after saline injection. Following training, cocaine was generalized to the cocaine training stimulus in a dose-dependent manner. Subsequently, guide cannulae were implanted bilaterally in the prefrontal cortex (from bregma, A = 2.7, L = 1.0, V = 3.0 mm), nucleus accumbens (A = 2.2, L = 1.5, V = 6 mm) or caudate putamen (A = 0.2, L = 2.5, V = 4). Injections were made via cannulae that extended 1 mm past the tip of the guide cannulae. Injection in the nucleus accumbens substituted for the IP training dose of cocaine in a dose-dependent manner with maximum generalization occurring with 10 micrograms of cocaine per side (87% cocaine-lever responding); in contrast, injections of cocaine in the prefrontal cortex or caudate-putamen produced only partial cocaine-lever responding (a maximum of 48 and 37% cocaine-lever responding, respectively). These data support the hypothesis of central mediation of the cocaine stimulus and show that cocaine administered in the nucleus accumbens is sufficient to produce the stimulus. The partial substitution of cocaine in the prefrontal cortex and caudate-putamen may reflect partial mediation of the cocaine stimulus in these brain areas.

Animals↗
PubMed1988

Substitution and cross-tolerance profiles of anorectic drugs in rats trained to detect the discriminative stimulus properties of cocaine.

Rats were trained to discriminate cocaine, 10.0 mg/kg, using a two-lever operant procedure. Dose-effect data were determined for the substitution of cocaine, diethylpropion, methylphenidate, phenmetrazine, phentermine, and fenfluramine for the cocaine stimulus. All of these drugs, except fenfluramine, substituted fully for the cocaine stimulus. Subsequently, training was halted and cocaine, 20 mg/kg/8 h, was administered for 9 days, and dose-effect data were redetermined for all of these drugs on days 7-9 of chronic administration. Chronic administration of cocaine produced tolerance to the stimulus properties of cocaine, and cross-tolerance to the stimulus properties of methylphenidate, phenmetrazine, and phentermine, such that doses approximately two-fold higher than those used acutely were necessary to reproduce the original effect; the potency for the substitution of diethylpropion for the cocaine stimulus was decreased greater than four-fold; and fenfluramine still failed to substitute for the cocaine stimulus. These data suggest that 1) a common mechanism may mediate tolerance to the discriminative stimulus properties of cocaine, methylphenidate, phenmetrazine, and phentermine, and 2) tolerance in the drug discrimination procedure may have potential for establishing a comprehensive evaluation of dependence liability of CNS stimulants.

Animals↗
PubMed1987

Anxiogenic properties of cocaine withdrawal.

Rats were trained to discriminate an injection of pentylenetetrazol (PTZ), 20 mg/kg, from saline using a two-lever operant procedure with food as a reinforcer. In substitution tests, rats selected the PTZ-appropriate lever after PTZ, but not after cocaine (20 mg/kg). A higher dose of cocaine (40 mg/kg) was behaviorally disruptive which resulted in no lever selection during the test session. Subsequently, training and testing were halted, and cocaine, 20 mg/kg/8-hr, was administered for 7 days. Following this chronic drug regimen, substitution of PTZ for the PTZ stimulus was increased. Furthermore, cocaine (40 mg/kg) substituted for the PTZ stimulus. Following redetermination of the PTZ and cocaine dose-response curves, chronic cocaine injections were terminated and spontaneous withdrawal was assessed by determining its substitution for the PTZ stimulus. Cocaine withdrawal progressively substituted for the PTZ stimulus reaching a peak 120 hrs after the last cocaine injection. Diazepam, 5 mg/kg, blocked the PTZ-like stimulus. These data demonstrate that 1) chronic administration of cocaine produced sensitization for the PTZ stimulus, 2) tolerance developed to the behaviorally disruptive effects of cocaine, and 3) cocaine withdrawal produced a PTZ-like stimulus which was blocked by diazepam.

Animals↗
PubMed1987

Evidence for dopaminergic involvement in tolerance to the discriminative stimulus properties of cocaine.

Rats were trained to discriminate cocaine, 10.0 mg/kg, in a two-lever operant procedure. Dose-effect data for generalization to cocaine and substitution of apomorphine for the cocaine stimulus were determined. Subsequently, training was halted and either apomorphine, 2.5 mg/kg per 8 h, or cocaine, 20 mg/kg per 8 h, was administered for 7-9 days. During chronic administration, the efficacy of cocaine and apomorphine as discriminative stimuli was decreased. These data suggest that dopaminergic mechanisms may mediate tolerance to the discriminative stimulus properties of cocaine.

Animals↗
PubMed1987

A method to shorten the training phase of drug discrimination.

Rats were trained to discriminate "drug" from "no drug" in a two-lever, food-reinforced task. One group was trained with cocaine (10 mg/kg) and a second group was trained with pentylenetetrazol (20 mg/kg). A method designed to shorten the time required for the training phase of drug discrimination experiments was assessed in subgroups for each drug. In one subgroup, single training sessions were conducted daily. In the other subgroup, a second session (either drug or saline) was conducted on days for which the first condition was saline. The training conditions were presented in an irregular sequence, with the same condition occurring in no more than two consecutive sessions. Rats trained by the accelerated method learned the discrimination in fewer days, with no decrement in acquisition per session, suggesting that drug discrimination training can be accomplished more rapidly by reducing inter-session interval.

Animals↗
PubMed1987

Evidence of a central mechanism mediating tolerance to the discriminative stimulus properties of cocaine.

Rats were trained to detect intraperitoneal (IP) administration of cocaine, 10.0 mg/kg, using a two-lever choice discrimination procedure. Following training, cocaine was generalized to the cocaine training stimulus in a dose-dependent manner. Subsequently, bilateral cannulae were implanted in the lateral ventricles in ten animals, and intracerebroventricular (ICV) administration of cocaine was also generalized to the IP training dose in a dose-dependent manner with maximum generalization occurring with 80 micrograms cocaine. After baseline testing, training was halted and cocaine, 20 mg/kg/8-hr, was injected chronically in all rats for 6 days, and then the dose-effect curve for generalization of cocaine was redetermined. Chronic administration of cocaine significantly shifted the dose-effect curve three-fold to the right for both IP and ICV routes of administration. These data suggest that the stimulus properties of cocaine administered centrally are generalized in rats trained by peripheral administration and supports the hypothesis of central mediation of the cocaine stimulus. Also, the comparable shift of the cocaine dose-effect curve following chronic cocaine administration suggests that a central pharmacodynamic mechanism mediates tolerance to the discriminative stimulus properties of cocaine.

Animals↗