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Biomedical subjects

J G Clement

Publications and source records attributed to J G Clement.

At least 37 records · Page 2Linked to original sources

Age-related changes in cortical porosity of the midshaft of the human femur.

Complete cross-sections from the femoral midshaft of 180 individuals of known height and weight, aged 21-97 y, from a modern Australian population were examined using automatic video image analysis to quantify total subperiosteal porosity (TSPP). More specifically, the aim was to investigate whether age changes were similar in both sexes in (1) total subperiosteal area (TSPA), cortical area (CA) and medullary area (MA), (2) intracortical porosity (ICP), and (3) the respective contributions to TSPP made by MA and intracortical void area (ICVA). Our findings indicated that both sexes showed a significantly greater height normalised TSPA in the 70s as compared with the 20s. Males had consistently larger bones with a greater height normalised CA. In both sexes CA showed a tendency to increase till the 7th decade and then to decline, more so in females. MA approximately trebled in females and doubled in males over the age range studied. Although ICP also increased, from 4-6% in young adults to over 9% in the elderly, it showed a significant difference between the sexes only in the 3rd decade, being greater in males at this stage. By contrast, TSPP became significantly greater in females (from that recorded in the 3rd decade) by the time they reached the 50s, while in males this did not occur till the 80s. It increased from approximately 25% in young adults of both sexes to approximately 50% in females and approximately 37% in males in their 80s. However, in the elderly there was great variability in both sexes in the appearance of bones from individuals of similar chronological age. Some bones differed little from those in younger subjects, others showed greatly increased ICP, still others displayed reduced cortical widths with low ICP. The femoral midshaft resembles other skeletal sites in that age changes in TSPP are more marked in females than males.

Adult↗

Development of a murine hypothermia model for study of respiratory tract influenza virus infection.

A hypothermia model was developed to predict mortality and morbidity caused by respiratory influenza virus infection in mice. To increase virulence, egg-propagated influenza A/PR/8 virus was adapted for growth in mice by four blind serial passages. The mouse-adapted influenza A virus was then used to infect groups of BALB/c mice via the intranasal route, and the 50% lethal dose (LD50) was determined. Rectal temperature of the infected mice was monitored daily, and survival rate was determined at day 14 after infection. The lowest average body temperature recorded in infected mice was approximately 10 degrees C below that in noninfected mice. In mice that developed hypothermia, with body temperature of 32 degrees C or lower, morbidity and mortality inevitably occurred. In this study, the LD50 and the 50% hypothermia-inducing dose (HID50) for mouse-adapted influenza A virus were compared and calculated to be at the same dose. These results suggest that the HID50 model could be used to predict mortality and morbidity associated with influenza virus infection in mice. This model could potentially be used to substantially reduce the time and extent of suffering inflicted on experimental animals due to viral infections, and therefore may serve as a more humane alternative to LD50 determinations.

Animals↗

Quantification of ethnic differences in facial profile.

The concept of facial aesthetics is becoming increasingly important and with the expanding application of orthodontic, orthognathic, plastic and reconstructive techniques to patients from continually diversifying ethnic backgrounds, it is timely that more elaborate methods for the evaluation of facial form are adopted. The aim of the present study was to further investigate the use of Fourier shape analysis in the quantification of facial profile and to investigate differences between racial groups. One hundred and twenty-two undergraduate dental students were photographed and surveyed for information pertaining to ethnic origin. Student's t-tests revealed significant differences (p < 0.05) in higher-order (fourth- and above) Fourier harmonics between male and female profiles, as well as between intervention and non-intervention groups. A comparison of multiple means test revealed significant differences (p < 0.05) in the third-order Fourier harmonic (vertex projection) between the Asian group and three other groups--Anglo-Celtic, Eastern European and Western European. Differences correlated with convexity in the lower third of the face, which was demonstrated by Fourier reconstruction.

Adolescent↗

Age trends in remodeling of the femoral midshaft differ between the sexes.

Cross-sectional area properties of the femoral midshaft from 203 individuals of known height and weight. 1-97 years of age, from a modern Australian population were quantified using automatic video image analysis. The aim of this study, taking height and weight into account, was to determine whether (a) age trends in remodeling differ between the sexes, (b) men are better able to compensate for bone loss with age, and (c) this protective mechanism is carried through into old age. Our findings indicated that during adulthood there are distinct gender differences in femoral remodeling. From around the third to the seventh decade, men showed a fairly uniform increase in subperiosteal area, polar moment of inertia, and medullary area. Women displayed two distinct phases during this period: relative stability until around the menopause and then a marked increase in all of the above variables. In old age, gender differences diminished, both sexes showing reduced periosteal apposition and increased endosteal resorption. The resultant decline in cortical area of approximately 4% in men and 15% in women from the third to the eighth decade was significant only in women. For a given height, men had larger, stiffer femoral shafts with a greater cortical width and area and maintained this advantage into old age. Diaphyseal bone was not immune from age-related changes affecting other skeletal sites: however, due to compensatory remodeling, which was particularly evident in men, this was not reflected in increased fracture rates.

Adolescent↗

Bone feature analysis using image processing techniques.

In order to establish the correlation between bone structure and age, and information about age-related bone changes, it is necessary to study microstructural features of human bone. Traditionally, in bone biology and forensic science, the analysis if bone cross-sections has been carried out manually. Such a process is known to be slow, inefficient and prone to human error. Consequently, the results obtained so far have been unreliable. In this paper we present a new approach to quantitative analysis of cross-sections of human bones using digital image processing techniques. We demonstrate that such a system is able to extract various bone features consistently and is capable of providing more reliable data and statistics for bones. Consequently, we will be able to correlate features of bone microstructure with age and possibly also with age related bone diseases such as osteoporosis. The development of knowledge-based computer vision-systems for automated bone image analysis can now be considered feasible.

Adult↗

Scanning electron microscope observations of incinerated human femoral bone: a case study.

Fragments of the incinerated remains of a fire victim were studied using scanning electron microscopy and microradiography. These observations were then compared with the heat-induced alterations found in laboratory heat-treated human bone. The incinerated bone fragments exhibited a range of colours, including black, grey and white, concomitant with alterations to the ultrastructure and microstructure of the bone tissue. The colour of the incinerated bone tissue, and the crystal habit and size associated with each region of colour, indicated a gradual decrease in the temperature attained in the bone, as a function of the radial distance from the outer cortical bone surface. A maximum temperature in the range approximately 1000-1200 degrees C had been attained in the outer cortical bone regions that were white in colour. A minimum temperature of 300 degrees C had been attained in the inner cortical bone regions that were black in colour. The period of time over which the fire attained the maximum temperature was inferred to be too short for the bone tissue to have reached an equilibrium with the surrounding environment, as the fire was due to a sudden ignition. However, the minimum temperature recorded was attained for a longer period of time as the organic contents of the Haversian canals and the medullary cavity had been completely combusted. From examinations of the spherical-type crystal size in the grey regions of cortical bone, the habit of the hexagonal-type crystals in the white regions of bone, and the preferred orientation of the mineralised collagen fibrils in the Haversian canals situated in the black regions of cortical bone, it was suggested that the deceased person was a young-to-mature adult, possibly aged 20-40 years.

Adult↗

Scanning electron microscope observations of heat-treated human bone.

This report describes the heat-induced alterations in human bone tissue observed using scanning electron microscopy and microradiography. Femoral bone samples were taken from persons varying in age from 1 year to 97 years at the time of their death. The bone was heated at selected temperatures in the range 200-1600 degrees C for periods of 2, 12, 18 and 24 h. Macroscopically, changes in colour occurred, together with some shrinkage, fracturing and distortion. However, dramatic changes occurred at the ultrastructural level. These changes included the progressive combustion of the organic portion of the bone tissue up to 400 degrees C and recrystallisation of the bone mineral beginning at 600 degrees C. Recrystallisation produced a range of crystal morphologies: spherical, hexagonal, platelets, rosettes and irregular. Crystal growth occurred at temperatures > 600 degrees C. Sintering led to fusion of crystals at 1000 degrees C. This process continued up to temperatures > 1400 degrees C. At 1600 degrees C the bone mineral melted. On heating, the morphology of crystals formed, and the ultrastructural changes which occurred, were found to be related to the age of the deceased, the temperature to which the bone had been heated and the duration of heating. These results are of importance to forensic scientists, arson investigators and paleoarcheologists in their investigation of cremated human bones, particularly when only fragments of bone are available, in order to determine something of the life history of the deceased and the circumstances surrounding the death.

Adolescent↗

A morphometric study of the cortex of the human femur from early childhood to advanced old age.

One hundred and ninety-five mid-shaft femoral bone samples were collected at the Victorian Institute of Forensic Pathology, Melbourne, Australia. These samples came from individuals aged 1-97 years, who had dies unexpectedly and were considered healthy immediately before death. From the samples, transverse sections 100-200 micronM thick were cut on a sawing microtome. Three groups of sections [from persons aged 19-21 (n = 9), 39-41 (n = 9), and 59-61 years (n = 9) at death] were adjusted to a thickness of 100 +/- 5 microns by hand-lapping and microradiographs were taken of these sections. Automatic image analysis methods were used to measure the area and perimeter of the femoral cortex for all 195 sections. Additionally, the number and areas of all holes within the cortex were measured for those sections that were microradiographed. The results show that, even though the number of Haversian canals measured from the entire bone cortex changes with age, the spread of values at any given age makes these measurements of limited value for age determination. From this it may be inferred that all methods that rely, to any extent, upon measurements of this parameter are likely to be flawed.

Adolescent↗

The acetylcholinesterase oxime reactivator HI-6 in man: pharmacokinetics and tolerability in combination with atropine.

In a double-blind, placebo-controlled, single-dose ascending pharmacokinetics and tolerance study, we evaluated the bispyridinium oxime HI-6 dichloride monohydrate (62.5, 125, 250, and 500 mg), administered intramuscularly with atropine sulphate, 2 mg, in 24 healthy male volunteers. The plasma HI-6 peak concentration (Cmax) and area under the concentration-time curve (AUC) demonstrated linear pharmacokinetics with low intradose variability, suggestive of uniformity of effect among subjects. HI-6 (500 mg) attained plasma drug concentrations that appeared adequate for practical use as an antidote. The mean +/- SD time to maximum plasma HI-6 concentration (tmax = 0.69 +/- 0.21 h, n = 16), and absorption half-life (t/2a = 0.17 +/- 0.05 h) indicated rapid onset of effect. The volume of distribution (Vd = 0.25 +/- 0.04 L kg-1 TBW) approximated the extracellular fluid volume. A high total body clearance (CL = 252 +/- 52 mL min-1) and short apparent elimination half-life (t/2e = 1.15 +/- 0.19 h) were expected for this polar quaternary ammonium drug. The renal clearance CLr = 137 +/- 33 mL min-1), which approximated the expected glomerular filtration rate, and 24 h urinary excretion of unchanged drug (55 +/- 10%) indicated substantial non-renal elimination. Blood pressure, heart rate, respiratory rate, electrocardiographic parameters, mental acuity, and vision were not altered. Adverse events and changes in serum, urine, and semen laboratory tests were mild. The pharmacokinetics, safety, and apparent efficacy of HI-6 suggest it may be a superior oxime antidote against nerve agent poisoning.

Adolescent↗

Age and temperature related changes to the ultrastructure and composition of human bone mineral.

This X-ray diffraction (XRD) investigation of heat-treated human femoral bone showed that the main mineral phase of both unheated bone and bone heated to 600 degrees C resembled that of a poorly crystalline form of hydroxyapatite. The rod-shaped apatite crystals in unheated bone persisted in bone heated up to 400 degrees C. Recrystallization at approximately 600 degrees C, produced larger crystals, which either retained their original morphology or changed to tabular or equidimensional shapes. The size of the apatite crystals in unheated and heated bone specimens was dependent on both temperature and age. When heated above 600 degrees C the crystallinity of the bone mineral increased, and the XRD pattern more closely resembled that of hydroxyapatite. Partial decomposition of the hydroxyapatite phase to calcium oxide above 1000 degrees C, and beta-tricalcium phosphate, alpha-tricalcium phosphate, and calcium oxide phosphate between 1200 degrees C and 1400 degrees C, indicated that the original apatite phase was both calcium deficient and contained carbonate. The relative peak intensities of the thermal decomposition products were related to some extent to the age of the deceased person and reflected the compositional changes that occur during bone aging. Because the thermally induced changes to the composition and ultrastructure of bone mineral were influenced by the age of the individual, this investigation proposed that the heat treatment of bone tissue may offer an alternative way of studying bone aging.

Adolescent↗

Computerized three-dimensional magnetic resonance imaging reconstructions of temporomandibular joints for both a model and patients with temporomandibular pain dysfunction.

The aim of this study was to assess computerized three-dimensional reconstruction of magnetic resonance images generated of a temporomandibular joint model and the temporomandibular joints of five patients with varying degrees of temporomandibular joint pain and dysfunction. The three-dimensional image reconstruction of an artificial temporomandibular joint model, consisting of a human dried skull and synthetic disk, was used to test the accuracy and reproducibility of the three-dimensional technique. It was found that computerized three-dimensional reconstruction improved the display format of magnetic resonance imaging by enabling multiple two-dimensional images in shades of grey to be viewed as one three-dimensional image with anatomic structures colored as desired. Further, by rotating this image, the anatomic relationships of the temporomandibular joint could be seen from any viewpoint. Volume measurements showed accuracy and reproducibility by independent operators. Computerized three-dimensional reconstruction was applied to the magnetic resonance images obtained from patients. They were used to assess magnetic resonance imaging technique and its applications for interpreting the clinical findings. Disk position, as revealed by the three-dimensional images, was found to correspond with the clinical assessment, except in two instances when the original, right-sided, magnetic resonance imaging was unclear. Three-dimensional reconstruction was simple to apply, required no patient involvement, and made multiple magnetic resonance images easier to interpret.

Adolescent↗

Osseointegration in sinus-forming bone.

Osseointegration, using bone-anchored titanium fixtures, is a well-established technique for both intraoral and craniofacial prosthetic rehabilitation. The use of this technique in children can be complicated by craniofacial growth and sinus development. This study evaluates the effects of sinus formation and growth on the fate of osseointegrated titanium fixtures in the growing porcine model. At 3 weeks of age, six Landrace White cross male pigs had a 3.75 x 3.0 mm titanium fixture (Noblepharma) inserted into their right frontal bone where the right frontal sinus would subsequently develop. Preoperative CT scans with three-dimensional reconstructions were used to determine the insertion site. To follow the effects of growth and sinus formation, CT scans with three-dimensional reconstructions and cephalometric radiographs were taken at 1, 3, 6, and 9 weeks postoperatively and at sacrifice. The pigs were sacrificed serially, and direct osteometric measurements were taken to determine skull symmetry. All skulls were sectioned, and osseointegration was determined clinically, radiologically, and histologically with light and scanning electron microscopy. Five of the six fixtures osseointegrated. There were no apparent growth disturbances due to the fixtures. As growth progressed, the osseointegrated fixtures submerged into the frontal bone in a posteroinferior direction to become completely intraosseous 14 weeks after insertion. As the frontal sinus pneumatized, the fixtures remained osseointegrated, but progressive amounts of the fixtures became exposed in the sinus. From this study it would appear that osseointegrated titanium fixtures do not have any effect on calvarial growth and gradually submerge into the growing bone. As sinus development ensues, the fixtures remain integrated but become partially exposed within the sinus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Chromodacryorrhea in rats: absence following soman poisoning.

Chromodacryorrhea is the secretion of so-called "bloody tears" from the harderian gland which nearly circumscribes the eye within the bony orbit. Direct-acting cholinergic agonists such as oxotremorine, carbachol, and pilocarpine caused chromodacryorrhea but nicotine did not. Atropine blocked chromodacryorrhea induced by systemic administration of direct-acting cholinergic agonists. Thus, chromodacryorrhea appears to be a muscarinic receptor-related event. Soman (pinacolyl methylphosphonofluoridate), a potent irreversible inhibitor of acetylcholinesterase which increases the synaptic concentration of the neurotransmitter acetylcholine, did not induce chromodacryorrhea in rats. Similarly, physostigmine, a tertiary, carbamate acetylcholinesterase inhibitor, did not induce chromodacryorrhea. In vivo soman-induced inhibition of harderian gland acetylcholinesterase was independent of the soman dose and the inhibition was significantly less than brain acetylcholinesterase. In vitro soman-induced inhibition of harderian gland acetylcholinesterase was not significantly different from that of diaphragm acetylcholinesterase. The lack of inhibition of acetylcholinesterase in the harderian gland does not appear to be due to a difference in sensitivity to inhibition by soman. The distribution of the various molecular forms of acetylcholinesterase between the diaphragm and harderian gland was different. There was a great deal more of the 4S form of acetylcholinesterase in the harderian gland than in the diaphragm. The lack of the following, inhibition of harderian gland acetylcholinesterase and elevation of the synaptic concentration of acetylcholine, could explain the absence of chromodacryorrhea following soman poisoning. The discrepancy between the significant soman-induced inhibition of brain acetylcholinesterase and the lack of inhibition of harderian gland acetylcholinesterase allows one to speculate that there may be a very efficient scavenger of soman present in the rat harderian gland.

Acetylcholinesterase↗

Toxicity of the combined nerve agents GB/GF in mice: efficacy of atropine and various oximes as antidotes.

The toxicity of a combination of isopropyl methylphosphonofluoridate (sarin; GB) and cyclohexyl methylphosphonofluoridate (GF) and the efficacy of various oxime reactivators in combination with atropine against the combined GB/GF challenge were evaluated in mice. The 24-h s.c. LD50 of the GB/GF combination was 1.15 mumol/kg (1.10-1.21; 95% confidence limits). Mice administered GB/GF displayed typical signs of nerve agent poisoning such as tremors and convulsions, with death most likely due to anoxia subsequent to respiratory arrest. The GB/GF LD50 value was comparable to the s.c. LD50 of 1.35 and 1.21 mumol/kg for GF and GB in mice, respectively. Combining the two nerve agents did not result in potentiation of the toxicity. In combination with atropine sulfate (17.4 mg/kg, i.p.), which alone did not reduce mortality, the oximes tested, 2-PAM, obidoxime and HI-6, were all effective when administered 5 min before 3 x LD50 dose of GB/GF with 24-h ED50 values of 102.5, 18.22 and 1.96 mumol/kg, respectively. Use of the GB/GF combination does not appear to confer any unique toxicity profile and appears to be easily treated with the standard therapy of a cholinolytic and oxime.

Animals↗

In vitro oxime-induced reactivation of various molecular forms of soman-inhibited acetylcholinesterase in striated muscle from rat, monkey and human.

The purpose of this study was to compare the in vitro reactivation of the various molecular forms of soman-inhibited acetylcholinesterase by oximes such as HI-6, toxogonin and PAM, in striated muscle tissue from three species-rat, monkey and human. To simulate the various in vivo conditions the oxime was present either 5 min before and after (Pre-Post) or 5 min after (Post) exposure to the nerve agent soman. In the Pre-Post mode the oxime effects would result from a combination of not only shielding of acetylcholinesterase from soman inhibition but also from immediate reactivation of soman-inhibited acetylcholinesterase. In the Post experimental group the increase in soman-inhibited acetylcholinesterase activity was due to reactivation. HI-6 (Pre-Post) increased significantly the activity of soman-inhibited acetylcholinesterase in the rat, human and monkey muscle. HI-6 (Post) was a highly effective reactivator of soman-inhibited acetylcholinesterase in the rat muscle and moderately so in the human and monkey muscle. Toxogonin (Pre-Post) and toxogonin (Post) were effective in increasing soman-inhibited acetylcholinesterase activity in rat muscle but were relatively ineffective in the human and monkey muscle. PAM (Pre-Post) and PAM (Post) were ineffective in increasing soman-inhibited acetylcholinesterase activity in muscle from all species examined. Effectiveness of oxime-induced reactivation of soman-inhibited acetylcholinesterase could be estimated from the total acetylcholinesterase activity which appears to reflect the results found with the individual molecular forms of acetylcholinesterase. In addition, SAD-128, a non-oxime bispyridinium compound, appeared to enhance significantly the HI-6 induced reactivation of soman-inhibited acetylcholinesterase in human but not rat striated muscle.

Acetylcholinesterase↗

Volumetric and visual assessment of the mesial temporal structures in Alzheimer's disease.

BACKGROUND: Alzheimer's disease is the commonest cause of dementia. Clinical diagnosis of Alzheimer's disease may be difficult. Magnetic resonance imaging has a role to play in diagnosis. AIM: To assess whether volumetric and/or visual assessment of the mesial temporal structures is useful in separating patients with Alzheimer's disease from age matched controls. METHODS: Twenty-four patients with Alzheimer's disease diagnosed by NINCDS/ADRDA criteria and 15 age matched controls were studied with magnetic resonance imaging (MRI) and volumetric techniques. Segmented volumes of the mesial temporal structures were assessed visually and volumetrically. RESULTS: Volumetric analysis demonstrated significant (p < .001) differences between the two groups, but showed overlap in individual cases. Discriminant function analysis predicted correct group membership (patient or control) in 85% of cases. Visual assessment alone demonstrated a sensitivity of 92% and a specificity of 93% in distinguishing the Alzheimer patients from controls. CONCLUSION: Volumetric and visual assessment of the mesial temporal structures is useful in separating Alzheimer patients from controls. Overlap is present in individual cases. Visual assessment was as useful in separating the two groups as the volumetric analysis.

Aged↗

Pharmacological nature of soman-induced hypothermia in mice.

The object of the study was to determine the pharmacological nature of pinacolyl methylphosphonofluoridate (soman)-induced hypothermia in mice. This was accomplished by examining the soman hypothermia dose response and the effect of various pharmacological antagonists in comparison to the hypothermia responses of muscarinic and nicotinic cholinergic agonists such as oxotremorine and nicotine and another anticholinesterase, physostigmine. Core temperature in mice was monitored by telemetry. In general, atropine antagonized oxotremorine, physostigmine, and soman hypothermia but not nicotine hypothermia whereas mecamylamine antagonized nicotine hypothermia but not that produced by the other agonists. Soman hypothermia was not affected significantly by various pharmacological antagonists, suggesting that other neurotransmitters were not involved in the expression of soman hypothermia. Soman hypothermia appears to be due to muscarinic receptor stimulation and can be effectively antagonized, but not completely, by the use of atropine. Acetylcholinesterase oxime reactivators, such as HI-6 and toxogonin, were ineffective in antagonizing soman-induced hypothermia and reactivating hypothalamic acetylcholinesterase, whereas HI-6 was effective in reactivating soman-inhibited diaphragm acetylcholinesterase when administered up to 10 min after soman, indicating that aging of the soman-inhibited acetylcholinesterase had not occurred. Soman hypothermia appears to be primarily a muscarinic receptor-related event.

Acetylcholinesterase↗

[Role of the Health Services Commissioner in the state of Victoria in Australia].

In 1988 a Health Commissioner (HSC) was established in Victoria, Australia. The role of the HSC is to apply the concept of social justice in the area of health care issues. The HSC is independent of the normal ministerial machinery of government and reports directly to the Victorian Parliament. The HSC is able to investigate complaints about all aspects of health care provision and attempts to settle disputes by conciliation rather than by recourse to the more cumbersome and expensive option of litigation. The HSC is also empowered to make recommendations which would reduce complaints in the future. Significant progress has been made and now similar schemes based on the successful Victorian model are being established elsewhere. At the same time financial constraints in Victoria are preventing the HSC from achieving its full potential as an agency to promote quality health care.

Delivery of Health Care↗