Biomedical subjects
Publications and source records attributed to P D Jones.
Peripheral nervous system complications of Q fever are uncommon. A case of electrophysiologically documented brachial neuritis occurring during acute Coxiella burnetii infection is reported. The relevant literature is reviewed.
In vitro cell bioassays are useful techniques for the determination of receptor-mediated activities in environmental samples containing complex mixtures of contaminants. The cell bioassays determine contamination by pollutants that act through specific modes of action. This article presents strategies for the evaluation of aryl hydrocarbon receptor (hereafter referred as dioxin-like) or estrogen receptor mediated activities of potential endocrine disrupting compounds in complex environmental mixtures. Extracts from various types of environmental or food matrices can be tested by this technique to evaluate their 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents or estrogenic equivalents and to identify contaminated samples that need further investigation using resource-intensive instrumental analyses. Fractionation of sample extracts exhibiting significant activities, and subsequent reanalysis with the bioassays can identify important classes of contaminants that are responsible for the observed activity. Effect-directed chemical analysis is performed only for the active fractions to determine the responsible compounds. Potency-balance estimates of all major compounds contributing to the observed effects can be calculated to determine if all of the activity has been identified, and to assess the potential for interactions such as synergism or antagonism among contaminants present in the complex mixtures. The bioassay approach is an efficient (fast and cost effective) screening system to identify the samples of interest and to provide basic information for further analysis and risk evaluation.
The environmental distribution of fluorinated organic compounds (FOCs) has been less well described than the other halogenated hydrocarbons such as chlorinated and brominated compounds. This is despite the fact that FOCs have been used in a wide variety of products and applications for more than 50 years. FOCs are resistant to hydrolysis, photolysis, microbial degradation, or metabolism by vertebrates due to the high energy of carbon-fluorine bond. In particular, perfluorinated (fully fluorinated) compounds (PFCs) have the potential to persist in the environment. But, until recently, the extent and magnitude of environmental distribution of PFCs was unknown. Recent development of an analytical technique for PFCs using high performance liquid chromatography-negative ion electrospray tandem mass spectrometry (HPLC-ESMSMS) permitted the survey of PFCs in livers and blood plasma of wildlife on a global scale.
Induced sputum using hypertonic saline (HS) is a useful research tool to study airway inflammation (AI). HS provocation testing can also be used to measure airway hyperresponsiveness (AHR). A combined HS challenge and sputum induction procedure has been developed to permit assessment of AI and AHR in a single test. The aim of this study is to report the success and tolerability of sputum induction alone, and in combination with a HS bronchial provocation challenge. Sputum induction alone was performed with beta2-agonist pretreatment. In the combined challenge, no beta2-agonist pretreatment was used. A high-output ultrasonic nebulizer with valve box and tubing were used to deliver 4.5% saline in doubling time periods from 0.5 s to 4 min. Outcomes assessed were completion of the test protocol, adequacy of sputum samples, decrease in FEV1, and adverse effects during the procedure. Fifty-three children who underwent a sputum induction alone, and 182 children who underwent a combined sputum induction and bronchial provocation using HS. Sputum induction alone was well tolerated, with 98% of children completing the procedure and only 4% experiencing a significant (> 15%) fall in FEV1. An adequate sample of sputum was obtained in 92% of children. The combined challenge was completed by 90% of children. A distressing cough occurred in 13% of children and irritation of the mucosa in 1% of children. In the combined challenge an adequate sample of sputum was obtained in significantly fewer children than with sputum induction alone (70% versus 92%, p < 0.05). Sputum cellular changes reflected the shorter nebulization time with sputum induction alone. We conclude that induction of sputum using HS after pretreatment with bronchodilator is well tolerated with a high success rate in children. Combining the HS challenge with sputum induction provides additional information and is a useful means of comparing AHR and AI simultaneously, but at the expense of having a reduced success rate in obtaining an adequate sample of sputum, as well as increased side effects.
Perfluorooctane sulfonate (PFOS) was measured in 161 samples of liver, kidney, blood, or egg yolk from 21 species of fish-eating water birds collected in the United States including albatrosses from Sand Island, Midway Atoll, in the central North Pacific Ocean. Concentrations of PFOS in the blood plasma of bald eagles collected fromthe midwestern United States ranged from 13 to 2,220 ng/mL (mean: 330 ng/mL), except one sample that did not contain quantifiable concentrations of PFOS. Concentrations of PFOS were greater in blood plasma than in whole blood. Among 82 livers from various species of birds from inland or coastal U.S. locations, Brandt's cormorant from San Diego, CA, contained the greatest concentration of PFOS (1,780 ng/g, wet wt). PFOS was also found in the sera of albatrosses from the central North Pacific Ocean at concentrations ranging from 3 to 34 ng/mL. Occurrence of PFOS in birds from remote marine locations suggests widespread distribution of PFOS and related fluorochemicals in the environment.
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Knowledge of past climate variability is crucial for understanding and modeling current and future climate trends. This article reviews present knowledge of changes in temperatures and two major circulation features-El Niño-Southern Oscillation (ENSO) and the North Atlantic Oscillation (NAO)-over much of the last 1000 years, mainly on the basis of high-resolution paleoclimate records. Average temperatures during the last three decades were likely the warmest of the last millennium, about 0.2 degrees C warmer than during warm periods in the 11th and 12th centuries. The 20th century experienced the strongest warming trend of the millennium (about 0.6 degrees C per century). Some recent changes in ENSO may have been unique since 1800, whereas the recent trend to more positive NAO values may have occurred several times since 1500. Uncertainties will only be reduced through more extensive spatial sampling of diverse proxy climatic records.
Perfluorooctane sulfonate (PFOS) is a perfluorinated molecule that has recently been identified in the sera of nonindustrially exposed humans. In this study, 247 tissue samples from 15 species of marine mammals collected from Florida, California, and Alaskan coastal waters; and northern Baltic Sea; the Arctic (Spitsbergen); and Sable Island in Canada were analyzed for PFOS. PFOS was detected in liver and blood of marine mammals from most locations including those from Arctic waters. The greatest concentrations of PFOS found in liver and blood were 1520 ng/g wet wt in a bottlenose dolphin from Sarasota Bay, FL, and 475 ng/mL in a ringed seal from the northern Baltic Sea (Bothnian Sea), respectively. No age-dependent increase in PFOS concentrations in marine mammals was observed in the samples analyzed. The occurrence of PFOS in marine mammals from the Arctic waters suggests widespread global distribution of PFOS including remote locations.
High-resolution proxies of past climate are essential for a better understanding of the climate system. Tree rings are routinely used to reconstruct Holocene climate variations at high temporal resolution, but only rarely have they offered insight into climate variability during earlier periods. Fitzroya cupressoides-a South American conifer which attains ages up to 3,600 years-has been shown to record summer temperatures in northern Patagonia during the past few millennia. Here we report a floating 1,229-year chronology developed from subfossil stumps of F. cupressoides in southern Chile that dates back to approximately 50,000 14C years before present. We use this chronology to calculate the spectral characteristics of climate variability in this time, which was probably an interstadial (relatively warm) period. Growth oscillations at periods of 150-250, 87-94, 45.5, 24.1, 17.8, 9.3 and 2.7-5.3 years are identified in the annual subfossil record. A comparison with the power spectra of chronologies derived from living F. cupressoides trees shows strong similarities with the 50,000-year-old chronology, indicating that similar growth forcing factors operated in this glacial interstadial phase as in the current interglacial conditions.
Concentrations of polychlorinated biphenyls (PCBs), DDTs (p,p'-DDE, p,p'-DDD, p,p'-DDT), chlordanes (CHLs; cis-chlordane, cis-nonachlor, trans-nonachlor, and oxychlordane), hexachlorocyclohexane isomers (HCHs), hexachlorobenzene (HCB), tris(4-chlorophenyl)methane (TCPMe), tris(4-chlorophenyl)methanol (TCPMOH), and mono- (MBT), di-(DBT), and tri-butyltin (TBT) were determined in blubber and livers of 15 California sea lions (Zalophus californianus), 6 northern elephant seals (Mirounga augustirostris), and 10 harbor seals (Phoca vitulina) found stranded along the coasts of California, USA, during 1991-1997. Among the organochlorines analyzed, DDTs were predominant, followed in decreasing order by PCBs, CHLs, TCPMe, TCPMOH, HCHs, and HCB. The greatest concentrations of organochlorines were found in California sea lions. The highest DDT and PCB concentrations found in the blubber of California sea lions were 2,900 and 1,300 microg/g, lipid weight, respectively. Concentrations of TCPMe and TCPMOH in California sea lions were correlated significantly with DDT concentrations. Concentration ratios of various organochlorines in harbor seal livers were different from those in California sea lions and elephant seals, which suggested that the sources of exposure of harbor seals to organochlorines were different from those in the other two species. Concentrations of butyltin compounds in livers of pinniped species ranged from 2 to 99 ng/g, wet weight, which were less than those observed in cetaceans and in California sea otters.
Human infection by Cryptococcus neoformans var. neoformans is well characterised and usually occurs in immunocompromised patients. Less is known about infection by Cryptococcus neoformans var. gattii, which usually produces disease in previously normal individuals. In two cases of human pulmonary infection by Cryptococcus neoformans var. gattii, we observed a mixed inflammatory pattern, including granulomas associated with numerous T lymphocytes and a lymphocytic interstitial pneumonitis with B lymphocytes and formation of follicles. We also established a murine model of pulmonary infection by Cryptococcus neoformans var. gattii, which reproduced most of these features. This model is likely to prove useful in studies of the pathogenesis of this infection.
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Rainbow trout were fed a diet containing 1.8, 18, or 90 pg/g 3H-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for up to 320 d. Concentrations of TCDD were determined in muscle, liver, and ovaries at 100, 150, 200, and 250 d. Concentrations of TCDD reached an apparent steady-state concentration in liver after 100 d of exposure, whereas concentrations in other tissues continued to increase until 150 d of exposure. The greatest portion of the total mass of TCDD was present in the muscle tissue with lesser proportions in other organs. As the ovaries developed before spawning, an increase occurred in the total mass of TCDD present in this tissue. The assimilation rate of TCDD during the initial 100 d of the exposure was determined to be between 10 and 30%. This is somewhat less than estimates derived based on both uptake and elimination constants determined during shorter exposures. Biomagnification factors (BMFs) were estimated for all tissues and exposure concentrations, and at all exposure periods. Lipid-normalized BMFs for muscle ranged from 0.38 to 1.51, which is consistent with the value of 1.0 predicted from fugacity theory. Uptake and depuration rate constants were determined and used to predict individual organ TCDD concentrations. Comparison with observed values indicated that the model could be used to predict tissue concentrations from the known concentrations of TCDD in food. This model will allow more refined risk assessments by predicting TCDD concentrations in sensitive tissues such as developing eggs.
The Rocky Mountain Arsenal (RMA), a Superfund site near Denver, Colorado, USA, has a history of various industrial processes that may have led to the release of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs). The PCDDs, PCDFs, and non-ortho- and mono-ortho-substituted PCBs cause a common set of toxic effects that are mediated through the aryl hydrocarbon receptor (AhR). The total AhR-mediated activity of complex mixtures in biota samples from the RMA and surrounding reference areas was determined by both instrumental and bioanalytical techniques. Mean concentrations of bioassay-derived 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TCDD-EQ) in carp eggs, owl livers, and kestrel eggs ranged from 0 to 8.5, 17 to 130, and 2.4 to 18 pg/g, respectively. For most samples analyzed, concentrations of TCDD-EQ and instrumentally derived TCDD equivalents (TEQs) were not significantly different. In a few tissue samples, concentrations of TEQs and TCDD-EQs were not equivalent. This can indicate the presence of AhR-active compounds that were not identified or quantified by instrumental techniques or the existence of nonadditive interactions among congeners when samples are analyzed by the bioassay. Overall, mean concentrations of TCDD-EQs in extracts of carp and kestrel eggs were not significantly different between groups of samples collected on and off the RMA, whereas concentrations of TCDD-EQs in several owl livers collected on the RMA were significantly greater than concentrations in owl livers from off the RMA.
OBJECTIVE: To study the palliative management of children dying on the wards of a tertiary referral centre. In particular to identify areas of difficulty and discuss ways in which these can be improved. METHODOLOGY: All children between the ages 1 and 19 years dying on the general paediatric wards of the John Hunter Children's Hospital (JHCH) (a tertiary referral centre in New South Wales Hunter Valley) between 1991 and 1998 were included in the study. The main outcome measures were the duration of 'terminal care only' treatment; time spent in hospital in the previous year; analgesia used, dose and route of administration; adjuvant medications; quality of life in the final 24 h. RESULTS: Eighteen children (aged between 1 and 19 years) died on the general paediatric wards at JHCH between 1991 and 1998. The most common diagnosis was malignancy (five patients), with cystic fibrosis, cerebral palsy and a degenerative neurological disorder each accounting for four patients, and one child had herpes simplex encephalitis. In all children the terminal nature of their condition was recognized and in all but three patients there was documentation of 'not for resuscitation' (NFR) orders following discussion with the child's parents. The mainstay of analgesia was an intravenous narcotic infusion with 11 (61%) children needing a morphine infusion. Fifteen patients (83%) required other medications including antiemetics, anticonvulsants and corticosteroids. Twelve (66%) children were semiconscious or unconscious on the day of death. Three children were uncomfortable and distressed, one alert and symptom free and in two cases the level of consciousness was not recorded. Three children continued to have seizures until their death. CONCLUSION: The majority of terminally ill children were managed well with intravenous narcotics and adjuvant medications. There may be scope for such children to be managed successfully at home with appropriate support for the general practitioner by paediatric and palliative care specialists. Some cases in which palliation is difficult do remain in hospital and additional measures need to be employed to ensure a symptom free death for these children.
The prevalence of asthma varies widely throughout the world. We now believe that asthma is due to airway inflammation caused by an imbalance of the T-lymphocytes in the airway. The atopy that drives asthma is due to a predominance of Th2 lymphocytes in the airway. This paper links the prevalence of asthma inversely to the prevalence of tuberculosis and enteric infection. We will argue that the reason we observe such marked variations in the prevalence of asthma around the world is the fact that in the developing world there is a survival advantage in the fetal immune response to mature from Th2 to Th1 lymphocyte predominant. A Th1 response is required to combat infectious diseases such as typhoid and tuberculosis. Data from the World Health Organization confirms that these two infectious diseases occur very rarely in those communities where the asthma is high. It may be that the clean and infection-free environment of Australia and New Zealand is responsible for the region of Oceania having the dubious honor of having the highest prevalence of asthma in the world.
Polychlorinated biphenyls (PCBs) are persistent, bioaccumulative and toxic contaminants in the environment. Individual PCB congeners exhibit different physico-chemical properties and biological activities which result in different environmental distributions and toxicity profiles. The variable composition of PCB residues in environmental matrices and their different mechanisms of toxicity, complicate the development of scientifically based regulations for the risk assessment. Various approaches for the assessment of risks of PCBs have been critically examined. Recent developments in the toxic equivalency factor (TEF) approach for the assessment of toxic effects due to dioxin-like PCBs have been examined. PCB exposure studies which describe non-dioxin-like toxic effects, particularly neuro-behavioral effects and their effective doses in animals were also considered. A comparative assessment of effective doses for dioxin-like and non-dioxin-like effects by PCBs was made to evaluate the relative significance of non-ortho and ortho-substituted PCBs in risk assessment. Using mink as an example, relative merits and implications of using TEF and total PCB approaches for assessing the potential for toxic effects in wildlife was examined.
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