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Biomedical subjects

R A James

Publications and source records attributed to R A James.

At least 37 records · Page 2Linked to original sources
PubMed2001

Diagnostic issues in unusual asphyxial deaths.

Upper airway occlusion may be due to a variety of causes and may result from accidents, suicides or homicides. Underlying natural diseases may also predispose to lethal choking episodes. A series of nine cases is reported to illustrate a range of circumstances that resulted in fatal upper airway compromise. These included suicide from upper airway obstruction due to an impacted blanket, and accidental deaths due to inhalation of soil, a rock, and a video cassette sticker. One death resulted from glottic obstruction due to a mucosal cavernous haemangioma, another from an enlarged tonsil, and two deaths were precipitated by underlying organic disease in the form of dementia and insulin-dependent diabetes mellitus. The manner of death was not clear cut in two cases where there was evidence of possible accidental death or suicide.

Journal Article↗
PubMed2001

Induction and time-dependent accumulation of micronuclei in peripheral blood of transgenic p53+/- mice, Tg.AC (v-Ha-ras) and parental wild-type (C57BL/6 and FVB/N) mice exposed to benzene by inhalation.

In this study, we determined the induction and time-dependent accumulation of micronuclei in the peripheral blood of transgenic C57BL/6 p53+/- mice (p53+/- mice), FVB/N Tg.AC v-Ha-ras mice (Tg.AC mice) and their isogenic parental strains, FVB/N and C57BL/6 following inhalation exposure to benzene. Our objective was to determine the impact of p53 heterozygosity in p53+/- mice and the v-Ha-ras transgene in Tg.AC mice on micronuclei induction following exposure to inhaled benzene. A flow cytometric technique that distinguishes micronucleated red blood cells (MN-RBC) from micronucleated reticulocytes (MN-RET) was used. Mice were exposed to 0, 100 or 200 p.p.m. benzene using three different exposure regimens that resulted in an equal weekly cumulative exposure (3000 p.p.m.x hours) to benezene: 100 p.p.m. for 6 h/day, 5 days/week, Monday to Friday (M-F); 100 p.p.m. for 10 h/day, 3 days/week, Monday, Wednesday, Friday (MWF); and 200 p.p.m. for 5 h/day, 3 days/week MWF. Significant elevations of MN-RBC and MN-RET were observed from 1 week exposure in all of the benzene-exposed groups that increased in a time-dependent manner for up to 13 weeks exposure. Fewer MN-RBC and MN-RET were induced in the 200 p.p.m. benzene exposure group than in mice exposed to 100 p.p.m. The reduction in the frequency of MN-RBC in the 200 p.p.m.x5 h benzene exposure group is probably due to metabolic saturation resulting in a lower bone marrow dose (concentration x time) than in the 100 p.p.m. exposure groups. No differences were observed in the frequency of MN-RBC or MN-RET in Tg.AC compared with the FVB/N isogenic controls. At certain time points the frequency of micronuclei was less in the heterozygous p53+/- mice than determined in the wild-type C57BL/6 isogenic parental strain. These results indicate that the heterozygous state in p53+/- mice, but not the v-Ha-ras transgene in Tg.AC mice can influence the induction of micronuclei by benzene.

Animals↗
PubMed2001

Influence of dietary manganese on the pharmacokinetics of inhaled manganese sulfate in male CD rats.

Concerns exist as to whether individuals with relative manganese deficiency or excess may be at increased risk for manganese toxicity following inhalation exposure. The objective of this study was to determine whether manganese body burden influences the pharmacokinetics of inhaled manganese sulfate (MnSO(4)). Postnatal day (PND) 10 rats were placed on either a low (2 ppm), sufficient (10 ppm), or high (100 ppm) manganese diet. The feeding of the 2 ppm manganese diet was associated with a number of effects, including reduced body weight gain, decreased liver manganese concentrations, and reduced whole-body manganese clearance rates. Beginning on PND 77 +/- 2, male littermates were exposed 6 h/day for 14 consecutive days to 0, 0.092, or 0.92 mg MnSO(4)/m(3). End-of-exposure tissue manganese concentrations and whole-body (54)Mn elimination rates were determined. Male rats exposed to 0.092 mg MnSO(4)/m(3) had elevated lung manganese concentrations when compared to air-exposed male rats. Male rats exposed to 0.92 mg MnSO(4)/m(3) developed increased striatal, lung, and bile manganese concentrations when compared to air-exposed male rats. There were no significant interactions between the concentration of inhaled MnSO(4) and dietary manganese level on tissue manganese concentrations. Rats exposed to 0.92 mg MnSO(4)/m(3) also had increased (54)Mn clearance rates and shorter initial phase elimination half-lives when compared with air-exposed control rats. These results suggest that, marginally manganese-deficient animals exposed to high levels of inhaled manganese compensate by increasing biliary manganese excretion. Therefore, they do not appear to be at increased risk for elevated brain manganese concentrations.

Administration, Inhalation↗
PubMed2001

Traditional punishment and unexpected death in Central Australia.

Three cases of traditional punishment in Central Australian Aboriginal men are presented in which the thighs were speared or stabbed as part of a "payback" system. In two cases, an unexpected effect of the stabbing or spearing was death due to severing of major leg vessels. The relationship between customary Aboriginal law and general law in Australia has not been clearly defined; however, these cases demonstrate that significant and untoward effects may result from traditional punishments. Pathologists working near traditional Australian Aboriginal communities may still encounter such injuries at autopsy.

Adult↗
PubMed2001

Characteristic features of suicidal drownings: a 20-year study.

A retrospective study of cases of drowning suicide was undertaken at the Forensic Science Centre in Adelaide, South Australia for the period April 1980 to March 2000. A total of 123 cases were found, with 76 males (age, 16-88 years; average, 50.5 years; standard deviation [SD], 20.1 years) and 47 females (age, 34-88 years; average, 60.6 years; SD, 13.9 years). There were 66 fresh water drownings and 57 saltwater drownings. Female victims were significantly older than male victims for both fresh water and saltwater drownings (P < .05 and P < .01, respectively). Deaths in young women were rare. No temporal trend in drowning suicides could be shown, with annual numbers varying from 0 to 12 cases (average, 6.15; median, 7). Women preferentially chose the ocean or bath to drown themselves in, whereas males chose rivers, ditches, and lakes. Swimming pools were rarely used for suicide in this population; alcohol use was not usual; and there was often a significant history of mental illness.

Adolescent↗
PubMed2001

Asphyxiation from shoulder seat belts: an unusual motor vehicle injury.

Two cases of accidental asphyxia caused by lap-shoulder seat belts are reported. Lethal neck injuries from shoulder seat belts are uncommon, and episodes of asphyxiation are even rarer. Positioning of the shoulder belt over the neck, short stature, and incapacitation from other injuries were predisposing factors to upper airway compromise in these cases.

Accidents, Traffic↗
PubMed2001

Potential confusion arising from materials presenting as possible human remains.

The accurate identification of human tissues is an important part of forensic science, but may be difficult when specimens are small, fragmented, or burned. A wide variety of materials may be submitted as human, including parts of animals and nonorganic materials. Two cases involving a plastic fetal skeleton and a rubber fetus are described, which were initially considered to represent human remains, thus initiating police investigations for possible concealed stillbirth or infanticide. In one case, the remains were so deceptively real in appearance that hospital personnel initiated fibroblast cultures from an "umbilical cord". A third case of mineral concretions that resembled a human hand is also described. These cases demonstrate that protocols should be in place for the rapid assessment of all suspected human remains by pathologists, so that nonhuman material can be rapidly excluded, and police investigations terminated.

Bone and Bones↗
PubMed2001

Respiratory tract toxicity in rats exposed to Mexico City air.

The rat has been used extensively as a health sentinel, indicator, or monitor of environmental health hazards, but this model has not been directly validated against human exposures. Humans in Mexico City show upper respiratory tract lesions and evidence of pulmonary damage related to their environmental inhalation exposure. In this study, male and female F344 rats were exposed (23 hr/day) in Mexico City to local Mexico City air (MCA)* for up to seven weeks. Controls were maintained at the same location under filtered air. Prior to these exposures, several steps were taken. First, the nasal passages of normal male rats shipped from the United States and housed in Mexico City were examined for mycoplasma infection; no evidence of infection was found. In addition, a mobile exposure and monitoring system was assembled and, with an ozone (O3) exposure atmosphere, was tested along with supporting histopathology techniques and analysis of rat nasal and lung tissues. Last, the entire exposure model (equipment and animals) was transported to Mexico City and validated for a three-week period. During the seven-week study there were 18 one-hour intervals during which the average O3 concentration of MCA in the exposure chamber exceeded the US National Ambient Air Quality Standard (NAAQS) of 0.120 ppm 03 (hourly average, not to be exceeded more than once per year). This prolonged exposure of healthy F344 rats to MCA containing episodically low to moderate concentrations of 03 (as well as other urban air pollutants) did not induce inflammatory or epithelial lesions in the nasal airways or lung as measured by qualitative histologic techniques or quantitative morphometric techniques. These findings agree with those of previous controlled O3 inhalation studies, but they are in contrast to reports indicating that O3-polluted MCA causes significant nasal mucosal injury in adults and children living in southwestern Mexico City. Taken together, these findings may suggest that human airways are markedly more susceptible to the toxic effects of MCA than are the airways of the F344 rat.

Air Pollutants↗
PubMed2000

Unexpected death in association with an occult posterior lingual abscess.

An 82 year old woman was found unexpectedly dead in bed on the day of admission to hospital for the investigation of difficulty breathing. During a barium swallow examination after admission she was thought to have aspirated contrast material. At autopsy a large posterior lingual abscess was found, with barium in the airways. Death was attributed to a combination of upper airway narrowing associated with the abscess, chronic lung disease and possible aspiration of barium. This case demonstrates an unusual sequence of events associated with localised upper airway sepsis. It also confirms the importance of careful examination of the upper aerodigestive tract at autopsy in individuals of all ages.

Journal Article↗
PubMed2000

Optic chiasmal herniation--an under recognized complication of dopamine agonist therapy for macroprolactinoma.

The initial presentation of macroprolactinoma with visual field impairment, especially in males, is well recognized. Successful treatment with dopamine agonist therapy is characterized by a reduction in hyperprolactinaemia and often rapid and progressive resolution of the visual impairment. A small proportion of patients may subsequently develop a secondary deterioration in both their visual fields and visual acuities despite normalization of prolactin levels and tumour shrinkage. When pituitary apoplexy can be excluded this may result from traction on the optic chiasm which is pulled down into the now partially empty sella. We report a series of seven patients in whom chiasmal traction is believed to be the cause of their secondary deterioration in visual acuity occurring after dopamine agonist therapy for macroprolactinoma. The clinical history of two patients both of whom had rapid resolution of field defect with bromocriptine therapy but subsequently developed a recurrence of their bitemporal hemianopia is detailed. In both patients MRI scanning showed not only tumour involution but also marked optic chiasm herniation into the pituitary fossa. Surgical treatment was considered too risky; but on reduction of bromocriptine dosage the field defect improved in both cases; there was a modest elevation of prolactin and a degree of tumour re-expansion. The latter is believed to have released tethering of the optic chiasm and/or its vascular supply and thus obviated the need for surgery. Regular monitoring of visual fields in patients with macroprolactinoma receiving medical treatment is therefore important. Early recognition of secondary field loss due to chiasmal herniation enables correction of the visual field loss by manipulation of the medical therapy.

Adult↗
PubMed2000

Early adolescent suicide: a comparative study.

A study was undertaken of suicides in children and adolescents aged 16 years and under in South Australia, (Australia), and in San Diego County (USA) from January 1985 to December 1997. In South Australia there were 48 cases of youth suicide, representing 2% of the total number of 2251 suicides over that time. There were 34 males and 14 females (age range 13 to 16 years; mean = 15.3 years), with 22 hangings (46%), six gunshot wounds (13%), five train deaths (10%), four drug overdoses (8%), four jumping deaths (8%), three self immolations (6%), three carbon-monoxide inhalations (6%) and one electrocution (2%). In San Diego County there were 70 cases, representing 1.6% of the total number of 4492 suicides. There were 48 males and 22 females (age range 11 to 16 years; mean = 14.7 years), with 41 gunshot wounds (59%), 21 hangings (30%), six drug overdoses (9%), and two jumping deaths (3%). Preferred methods of suicide differed between the two areas, with significantly more gunshot suicides in San Diego compared to South Australia. The methods of suicide also differed in South Australia from older age groups, with more hangings, jumping deaths and self immolations, and fewer firearm and carbon monoxide inhalation deaths. Suicides in adolescents under the age of 17 years in both populations were, however, rare, with no demonstrable increase in numbers over the time of the study.

Journal Article↗
PubMed2000

Fractures of the hyoid bone and laryngeal cartilages in suicidal hanging.

A prospective study of neck trauma associated with suicidal hanging was undertaken at the Forensic Science Centre, Adelaide over a 3-year period from July 1996 to June 1999. There were a total of 40 cases of suicidal hanging with an age range of 17-74 years (average = 35 years; M:F = 33:7). Fractures of neck structures were identified in 19 cases (47.5%) and were more common in older victims and males. Nine victims had only thyroid cartilage fractures (22.5%), four victims had only fractures of the hyoid bone (10%), and six victims had fractures of both the hyoid bone and thyroid cartilage (15%). No fractures of the cricoid cartilage or cervical spine were demonstrated. Potentially confusing issues encountered in the assessment of possible fractures of neck structures included cases where there was congenital absence of the greater horn of the thyroid cartilage, where accessory nodules of cartilage were present in the posterior margin of the thyrohyoid membrane, and where there had not yet been bony fusion of the cartilaginous joints between the greater horns and body of the hyoid bone.

Journal Article↗
PubMed2000

The effect of thyroid hormone and a long-acting somatostatin analogue on TtT-97 murine thyrotropic tumors.

Thyroid hormone inhibits thyrotropin (TSH) production and thyrotrope growth. Somatostatin has been implicated as a synergistic factor in the inhibition of thyrotrope function. We have previously shown that pharmacological doses of thyroid hormone (levothyroxine [LT4]) inhibit growth of murine TtT-97 thyrotropic tumors in association with upregulation of somatostatin receptor type 5 (sst5) mRNA and somatostatin receptor binding. In the current study, we examined the effect of physiological thyroid hormone replacement alone or in combination with the long-acting somatostatin analogue, Sandostatin LAR, on thyrotropic tumor growth, thyrotropin growth factor-beta (TSH-beta), and sst5 mRNA expression, as well as somatostatin receptor binding sites. Physiological LT4 replacement therapy resulted in tumor shrinkage in association with increased sst5 mRNA levels, reduced TSH-beta mRNA levels and enhanced somatostatin receptor binding. Sandostatin LAR alone had no effect on any parameter measured. However, Sandostatin LAR combined with LT4 synergistically inhibited TSH-beta mRNA production and reduced final tumor weights to a greater degree. In this paradigm, Sandostatin LAR required a euthyroid status to alter thyrotrope parameters. These data suggest an important interaction between the somatostatinergic system and thyroid hormone in the regulation of thyrotrope cell structure and function.

Animals↗
PubMed2000

Pathologic features of childhood pedestrian fatalities.

A retrospective analysis of 68 cases of fatal childhood pedestrian accidents in South Australia that occurred over a 20-year period from January 1977 to December 1996 was undertaken. The age range was 12 months to 16 years (average, 7.6 years), with a male to female ratio of 41:27. The most common site of significant injury was the head (91.2%), followed by the abdomen (50%), chest (47.1%), and neck (38.2%). The most frequently encountered significant injury combinations involved the head, chest, and abdomen (14.7%); the head and chest (11.8%); and the head, neck, and abdomen (11.8%). Injuries were severe, consisting of extensive compound and comminuted skull fractures, neck fractures, and massive intraparenchymal brain and internal organ damage with avulsions and fragmentation. Non-life-threatening limb injuries occurred in 88% of cases. A distinct subgroup involved infants and younger children playing in driveways at home who were hit by reversing vehicles. The injuries were often of such a severe nature that death was instantaneous and with no possibility of successful medical intervention. More deaths occurred during the winter than summer months.

Abdominal Injuries↗
PubMed2000

Methadone maintenance programs--a two-edged sword?

Retrospective review was undertaken of all autopsies in which methadone was detected at the Forensic Science Centre, South Australia, during a 3-year period from July 1996 to June 1999. Thirty-five cases were found in which methadone had either caused or contributed to death (age range = 14-54 years; average = 31 years; M:F = 3.4:1). Ten victims were participating in a methadone maintenance program, of whom four died within a week of enrollment. Eight victims (23%) not enrolled in a methadone maintenance program were found who had died after the use of "diverted" methadone (i.e., prescribed for someone else) (age range = 14-34 years; average = 25 years; M:F = 6:2). Deaths were directly attributable to methadone toxicity in seven of the eight cases, with additional drugs or alcohol being found in seven cases. Prevention of ongoing deaths caused by methadone diversion could be achieved by allowing only daily releases of methadone, with the addict having to consume the drug under close supervision.

Adolescent↗
PubMed2000

Association analysis of the cytotoxic T lymphocyte antigen-4 (CTLA-4) and autoimmune regulator-1 (AIRE-1) genes in sporadic autoimmune Addison's disease.

Although autoimmune Addison's disease (AAD) may occur as a component of the monogenic autoimmune polyendocrinopathy type 1 syndrome (APS1), it is most commonly found as an isolated disorder or associated with the autoimmune polyendocrinopathy type 2 syndrome (APS2). It is likely that sporadic (non-APS1) AAD is inherited as a complex trait; however, apart from the major histocompatibility complex, the susceptibility genes remain unknown. We have examined polymorphisms at two non-major histocompatibility complex candidate susceptibility loci in sporadic (non-APS1) AAD: the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene and the autoimmune regulator (AIRE-1) gene. DNA samples from AAD subjects (n = 90) and local controls (n = 144 for CTLA-4; n = 576 for AIRE-1) were analyzed for the CTLA-4A/G polymorphism in exon 1 of the CTLA-4 gene and for the common mutant AIRE-1 allele (964de113) in United Kingdom subjects with APS1, by using the restriction enzymes Bst7II and BsrBI, respectively. There was an association of the G allele at CTLA-4A/G in AAD subjects (P = 0.008 vs. controls), which was stronger in subjects with AAD as a component of APS2 than in subjects with isolated AAD. In contrast, the mutant AIRE-1 964del13 allele was carried in one each of the 576 (0.2%) control subjects and the 90 (1.1%) AAD subjects as a heterozygote (P = 0.254, not significant), suggesting that this common AIRE-1 gene abnormality does not have a major role in sporadic (non-APS1) AAD.

Abatacept↗