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Biomedical subjects

P D Jones

Publications and source records attributed to P D Jones.

At least 19 recordsLinked to original sources

A 7-year review of deaths on the general paediatric wards at John Hunter Children's Hospital, 1991-97.

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.

Adolescent↗

The prevalence of asthma appears to be inversely related to the incidence of typhoid and tuberculosis: hypothesis to explain the variation in asthma prevalence around the world.

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.

Asthma↗

Dioxin-like and non-dioxin-like toxic effects of polychlorinated biphenyls (PCBs): implications for risk assessment.

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.

Animals↗

Chemotherapy reduces the prevalence of asthma symptoms in children with cancer: implications for the role of airway inflammation in asthma.

OBJECTIVE: Asthma is common in Australian children, with a prevalence of 30%. Airway inflammation is an important determinant of asthma symptoms. Chemotherapy used for the treatment of many childhood cancers suppresses inflammation. The prevalence of asthma symptoms in children treated with chemotherapy is unknown. METHODOLOGY: We therefore performed a survey of symptoms of asthma in children attending the oncology clinic at John Hunter Children's Hospital during the first 6 months of 1996. RESULTS: Fifty children aged 1-17 years were surveyed. Thirty-two of the children were in remission and had completed treatment with chemotherapy and 18 were currently undergoing treatment with chemotherapy. There was no significant difference in the prevalence of asthma in children before, during and after chemotherapy (26%, 22% and 34%), or in the prevalence of asthma in their siblings (28%). No child was classified as having persistent asthma while on chemotherapy and there was a significant reduction in the requirement for preventive asthma drugs 12% versus 0% (P = 0.03) being reported during chemotherapy. CONCLUSION: The prevalence of asthma in children who develop cancer is similar to their siblings and the same as the population as a whole. While asthma symptoms do not disappear completely during chemotherapy, the severity of asthma symptoms is less, with no need for asthma preventive treatment. The immunosuppressive side effects of the chemotherapy used in the treatment of childhood cancer appear to induce a remission in asthma symptoms. The ongoing requirement for bronchodilator therapy in patients whilst on chemotherapy suggests airway hyperreactivity persists in children while they are on chemotherapy. Prospective study of the airways of this group of patients promises to provide insights into the relationships between airway hyperreactivity, airway inflammation and asthma.

Adolescent↗

Chemotherapy for malignancy induces a remission in asthma symptoms and airway inflammation but not airway hyperresponsiveness.

Inflammation with infiltrations of eosinophils and mast cells into the walls of airways is considered to increase airway hyperresponsiveness (AHR), which in turn characterizes asthma. We present a child with AHR in whom the clinical course of asthma was related to eosinophilic bronchitis. Our patient was admitted at age 6 months with bronchiolitis and at age 4 years with asthma. Inhaled corticosteroids were begun at age 7 years. At age 8 he developed a meningeal sarcoma. While on chemotherapy, his asthma symptoms resolved and he no longer required prophylactic asthma treatment. After 14 months off all chemotherapy, he again had mild episodic asthma. While receiving chemotherapy for malignancy, he had an admission with a coagulase negative staphylococcal bacteremia. During sputum induction with 4.5% saline, he developed cough, wheeze, and a 20% reduction in peak expiratory flow (220 to 180 L/min) that reversed after treatment with salbutamol. The sputum cell count was 1.7 x 10(6)/ml with 1.1 x 10(6) being neutrophils. Two weeks later and prior to the induction of the second sputum, a 21% increase in FEV1 was recorded after bronchodilator inhalation (82% to 99% of predicted). The second sputum contained 2.7 x 10(6)/ml cells with 1.6 x 10(6)/ml neutrophils. Neither eosinophils nor mast cells were identified in the sputum. A third sputum obtained 14 months after the cessation of chemotherapy showed a sputum cell count of 16 x 10(6)/ml, with 11.6 x 10(6) neutrophils and 0.4 x 10(6) eosinophils; no mast cells were detected. A reversible 15% reduction in FEV1 was detected on hypertonic saline challenge testing. This boy had persistent airway hyperreactivity and reversible airways obstruction on three occasions during and following chemotherapy. When he developed asthma symptoms, his sputum contained neutrophils and eosinophils; while on chemotherapy his sputum did not contain eosinophils and he was symptom-free and off all asthma therapy. One can speculate that chemotherapy for malignancy can induce a remission in asthma symptoms but not AHR, and remission in symptoms is associated with a lack of eosinophilic or mast cell infiltrates in the sputum.

Asthma↗

Suspected infection in children with cancer.

The microbiology and severity of suspected infections in children with cancer admitted to the John Hunter Children's Hospital was determined in order to assess whether any alteration to the infection treatment protocol was required. All children with cancer aged 1-17 years who had an episode of suspected or proven infection that required parenteral treatment at John Hunter Children's Hospital (JHCH) during 1994/95 were reviewed. Thirty-seven children were treated for cancer at JHCH; 62 admissions for suspected infection which involved 26 children were reviewed. Sixteen of these children had a permanent central line. Children with a central line had an increase in the number of days of inpatient treatment required for the treatment of suspected infection, and they had more episodes of infection. A pathogen was isolated more frequently with blood cultures being positive more often and gram-positive species were methicillin resistant more often. These differences were not statistically significant. A pathogen was isolated in 52% of admissions. Sixteen pathogens were gram positive; 12 were gram negative, two were fungal and two were viral. Blood cultures were positive in 21 of 62 admissions, skin swabs in four admissions, urine cultures in three admissions, stool in two admissions and one species was isolated from an epidural catheter tip and from the sputum. In 16% of admissions, the identified organism was resistant to the initial empirical therapy of tobramycin and piperacillin. In a further 13%, flucloxacillin was added to the empirical regimen when a sensitive Staphylococcus was identified. No significant differences between the culture-negative and culture-positive groups were observed in admission pulse, fever or admission neutrophil count. However, those patients with a central line had a higher incidence of having a pathogen isolated if their temperature was > 39.5 degrees C. The median length of stay was longer for patients with a pathogen isolated on blood culture. Admission blood cultures were positive in 53% of admissions with an initial neutrophil count > 1000 x 10(9)/mL. Each of these children had a central line. Only one child died of infection during the 2-year study period. This review supports the observations that gram-positive infection is now more common than gram-negative infection in children with cancer. Despite the management advantages a permanent central line affords it is clear those children with a central line have an increased rate of infection and there needs to be caution in their use. The most important is the observation that any fever > 39.5 degrees C in a child with a central line is likely to be associated with a documented infection irrespective of the neutrophil count. The clinical outcomes observed in the present study indicate that tobramycin and piperacillin are effective empirical treatments for suspected infection in children with cancer.

Adolescent↗

Necrotizing cutaneous infection caused by Curvularia brachyspora in an immunocompetent host.

A case of necrotizing cutaneous infection in an immunocompetent host caused by the dematiaceous fungus, Curvularia brachyspora is presented. A 58-year-old man was transferred to the Prince Henry Hospital for treatment of necrotizing cellulitis involving both thighs that developed following cryotherapy. The patient did not respond to antibacterial therapy and hyperbaric oxygen. He was empirically commenced on intravenous amphotericin B and began to respond even before the pathogen C. brachyspora was identified.

Cellulitis↗

Effects induced by feeding organochlorine-contaminated carp from Saginaw Bay, Lake Huron, to laying White Leghorn hens. I. Effects on health of adult hens, egg production, and fertility.

This study was conducted to determine the effects of consumption of halogenated hydrocarbon compounds, primarily polychlorinated biphenyls (PCBs), contained in Great Lakes fish by the domestic chicken (Gallus domesticus). In this article we report the results of feeding White Leghorn hens for a period of 8 wk diets that contained 31-35% ocean fish and/or carp (Cyprinus carpio) from Saginaw Bay, Lake Huron, MI, which provided 0.3 (control), 0.8 (low-dose group), or 6.6 (high-dose group) mg PCB/kg, wet weight (ww). These concentrations were analogous to 3.3, 26, or 59 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents (TEQs)/g diet, ww, respectively. There were no significant effects on feed consumption among the groups. An unexpectedly high incidence of fatty liver hemorrhagic syndrome (FLHS) was observed in hens from the control (78% FLHS) and low-dose (75% FLHS) groups when compared to the high-dose group (15% FLHS). Birds in the control and low-dose groups had a significant increase in liver and body weights. Significant decreases in egg production, weight, and fertility were immediate in all dose groups, with the effect being permanent in the control and low-dose groups. Although the incidence of FLHS was an unexpected complication, the fact that there were no significant effects on egg production, egg weights, or fertility in the high-dose group suggests that the no-observable-adverse-effect concentration (NOAEC) for these parameters is in excess of 26 mg total weathered PCBs/kg egg, ww. This value was the average concentration of PCBs in the high-dose group eggs during the last week of the study.

Analysis of Variance↗

Effects induced by feeding organochlorine-contaminated carp from Saginaw Bay, Lake Huron, to laying White Leghorn hens. II. Embryotoxic and teratogenic effects.

Carp from Saginaw Bay, Lake Huron, MI, was fed to White Leghorn chickens for a period of 8 wk. The diets contained 0.3 (control; 0% carp), 0.8 (3.4% carp), and 6.6 (35% carp) mg polychlorinated biphenyls (PCBs)/kg diet, by wet weight (ww). These concentrations corresponded to 3.3, 26, and 59 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) equivalents/g diet ww, respectively. Though the diets were not acutely toxic to the adult laying hens, dose- and time-dependent responses were observed in the embryos and chicks. Toxicity was manifested as a dose-dependent increase in embryo mortality and decreased hatching rates. Furthermore, embryos and chicks displayed various deformities, including (1) head and neck edema and hemorrhage, (2) abdominal edema and hemorrhage, (3) foot and leg deformities, (4) skull and brain deformities, (5) yolk-sac deformities, and (6) miscellaneous deformities. The types of deformities observed were similar to those reported for embryos and chicks of colonial waterbirds in Saginaw Bay, as well as in controlled studies where technical mixtures or individual congeners of polychlorinated diaromatic hydrocarbons (PCDAHs) were fed to chickens. Increasing concentrations of carp also significantly affected the various organ weights in 18-d embryos and hatched chicks. At 18 d of incubation, weights of the embryos' livers were directly proportional to the concentration of PCBs in the diets. The weights of the spleens and bursae were inversely proportional to the dietary PCB concentration. After 3 additional days of incubation, significant effects in body, brain, liver, heart, and bursa weights were observed in hatched chicks. The concentrations of total PCBs, as well as 2,3,7,8-TCDD equivalents (TEQs) in the diets, were in the range of those that have been shown to cause similar adverse effects in other species. This study has shown that fish, the primary food source of colonial waterbirds in Saginaw Bay, are capable of causing adverse reproductive effects in a model avian species, the chicken. However, due to differences in the relative potency to cause effects on different endpoints in different species, the results of this study should not be used to predict the threshold for effects in other species.

Abnormalities, Multiple↗

Dietary exposure of mink to carp from Saginaw Bay, Michigan: 2. Hematology and liver pathology.

The effects of consumption of environmental contaminants contained in carp (Cyprinus carpio) from Saginaw Bay, Michigan on various hematological parameters and liver integrity of adult female mink (Mustela vision) were determined. Mink were fed diets that contained 0 (control), 10, 20, or 40% carp prior to and throughout the reproductive period (182 days). The diets contained 0.015, 0.72, 1.53, and 2.56 mg polychlorinated biphenyls (PCBs)/kg diet and 1.0, 19, 40, and 81 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQs)/g diet, respectively. Mink fed the diets containing carp showed a general dose-dependent occurrence of clinical signs commonly associated with chlorinated hydrocarbon toxicity, including listlessness, nervousness when approached, anorexia, and melena. Erythrocyte counts were less in mink exposed to Saginaw Bay carp than in controls, while the number of white blood cells was greater than in controls. Significant differences (p < 0.05) in the concentrations of neutrophils, lymphocytes, monocytes, and eosinophils were also found between the control and carp-fed groups, but are considered to be of limited clinical or biological importance. Hematocrit values for the mink fed the 20 and 40% carp diets were significantly less than those of mink in the control and 10% carp groups. There were no significant differences in hemoglobin concentrations among the groups. Necropsies revealed enlarged yellowish livers in many of the carp-fed mink, especially those fed the 40% carp diet. Liver, spleen, and lung weights of carp-fed mink were significantly greater than those of control mink.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Dietary exposure of mink to carp from Saginaw Bay, Michigan. 1. Effects on reproduction and survival, and the potential risks to wild mink populations.

Carp (Cyprinus carpio) collected from Saginaw Bay, Michigan, containing 8.4 mg total polychlorinated biphenyls (PCBs)/kg and 194 ng of 2,3,7,8-tetrachloro-dibenzo-p-dioxin equivalents (TEQs)/kg, were substituted for marine fish at levels of 0, 10, 20, or 40% in the diets of adult ranch mink (Mustela vison). The diets, containing 0.015, 0.72, 1.53, and 2.56 mg PCBs/kg diet, or 1.03, 19.41, 40.02, and 80.76 ng TEQs/kg diet, respectively, were fed to mink prior to and throughout the reproductive period to evaluate the effects of a naturally-contaminated prey species on their survival and reproductive performance. The total quantities of PCBs ingested by the mink fed 0, 10, 20, or 40% carp over the 85-day treatment period were 0.34, 13.2, 25.3, and 32.3 mg PCBs/mink. respectively. The corresponding quantities of TEQs ingested by the mink over the same treatment period were 23, 356, 661, and 1,019 ng TEQs/mink, respectively. Consumption of feed by mink was inversely proportional to the PCB and TEQ content of the diet. The diet containing Saginaw Bay carp caused impaired reproduction and/or reduced survival of the kits. Compared to controls, body weights of kits at birth were significantly reduced in the 20 and 40% carp groups, and kit body weights and survival in the 10 and 20% carp groups were significantly reduced at three and six weeks of age. The females fed 40% carp whelped the fewest number of kits, all of which were stillborn or died within 24 hours. Lowest observable adverse effect levels (LOAEL) of 0.134 mg PCBs/kg body weight/day or 3.6 ng TEQs/kg body weight/day for adult female mink were determined. The potential effects of exposure of wild mink to contaminated Great Lakes fish were assessed by calculating "maximum allowable daily intakes" and "hazard indices" based on total concentrations of PCB residues in several species of Great Lakes fish and mink toxicity data derived from the study.

Animals↗