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Biomedical subjects

M Feeley

Publications and source records attributed to M Feeley.

At least 19 recordsLinked to original sources

Human health implications of environmental contaminants in Arctic Canada: A review.

The objectives of this paper are to: assess the impact of exposure to current levels of environmental contaminants in the Canadian Arctic on human health; identify the data and knowledge gaps that need to be filled by future human health research and monitoring; examine how these issues have changed since our first assessment [Van Oostdam, J., Gilman, A., Dewailly, E., Usher, P., Wheatley, B., Kuhnlein, H. et al., 1999. Human health implications of environmental contaminants in Arctic Canada: a review. Sci Total Environ 230, 1-82]. The primary exposure pathway for contaminants for various organochlorines (OCs) and toxic metals is through the traditional northern diet. Exposures tend to be higher in the eastern than the western Canadian Arctic. In recent dietary surveys among five Inuit regions, mean intakes by 20- to 40-year-old adults in Baffin, Kivalliq and Inuvialuit communities exceeded the provisional tolerable daily intakes (pTDIs) for the OCs, chlordane and toxaphene. The most recent findings in NWT and Nunavut indicate that almost half of the blood samples from Inuit mothers exceeded the level of concern value of 5 microg/L for PCBs, but none exceeded the action level of 100 microg/L. For Dene/Métis and Caucasians of the Northwest Territories exposure to OCs are mostly below this level of concern. Based on the exceedances of the pTDI and of various blood guidelines, mercury and to a lesser extent lead (from the use of lead shot in hunting game) are also concerns among Arctic peoples. The developing foetus is likely to be more sensitive to the effects of OCs and metals than adults, and is the age groups of greatest risk in the Arctic. Studies of infant development in Nunavik have linked deficits in immune function, an increase in childhood respiratory infections and birth weight to prenatal exposure to OCs. Balancing the risks and benefits of a diet of country foods is very difficult. The nutritional benefits of country food and its contribution to the total diet are substantial. Country food contributes significantly more protein, iron and zinc to the diets of consumers than southern/market foods. The increase in obesity, diabetes and cardiovascular disease has been linked to a shift away from a country food diet and a less active lifestyle. These foods are an integral component of good health among Aboriginal peoples. The social, cultural, spiritual, nutritional and economic benefits of these foods must be considered in concert with the risks of exposure to environmental contaminants through their exposure. Consequently, the contamination of country food raises problems which go far beyond the usual confines of public health and cannot be resolved simply by risk-based health advisories or food substitutions alone. All decisions should involve the community and consider many aspects of socio-cultural stability to arrive at a decision that will be the most protective and least detrimental to the communities.

American Indian or Alaska Native↗

Direct thrombin injection into aneurysmal sac in a patient with a type II endoleak.

Endovascular grafting of abdominal aortic aneurysms provides a good alternative to open surgery, especially in high-risk patients. Endoleaks are a well-recognized complication and are typically diagnosed on CT. We describe a case in which a patient's endoleak was evaluated by MRI and successfully treated by direct thrombin injection into the site of the leak.

Aged↗

Effects of caffeine on human health.

Caffeine is probably the most frequently ingested pharmacologically active substance in the world. It is found in common beverages (coffee, tea, soft drinks), in products containing cocoa or chocolate, and in medications. Because of its wide consumption at different levels by most segments of the population, the public and the scientific community have expressed interest in the potential for caffeine to produce adverse effects on human health. The possibility that caffeine ingestion adversely affects human health was investigated based on reviews of (primarily) published human studies obtained through a comprehensive literature search. Based on the data reviewed, it is concluded that for the healthy adult population, moderate daily caffeine intake at a dose level up to 400 mg day(-1) (equivalent to 6 mg kg(-1) body weight day(-1) in a 65-kg person) is not associated with adverse effects such as general toxicity, cardiovascular effects, effects on bone status and calcium balance (with consumption of adequate calcium), changes in adult behaviour, increased incidence of cancer and effects on male fertility. The data also show that reproductive-aged women and children are 'at risk' subgroups who may require specific advice on moderating their caffeine intake. Based on available evidence, it is suggested that reproductive-aged women should consume </=300 mg caffeine per day (equivalent to 4.6 mg kg(-1) bw day(-1) for a 65-kg person) while children should consume </=2.5 mg kg(-1) bw day(-1).

Abnormalities, Drug-Induced↗

Health risks to infants from exposure to PCBs, PCDDs and PCDFs.

Global contamination by a variety of anthropogenic persistent organic chemicals, such as dioxins and PCBs, has resulted in human exposure throughout all phases of development. Detectable concentrations of PCBs and dioxins have been found in amniotic fluid, placenta and foetal tissue samples while infants who are breast-fed can obtain blood levels greater than those of their mother's. In two separate food poisoning episodes where infants were exposed in utero to elevated levels of heat-degraded PCBs (PCBs, PCQs, PCDFs), a variety of adverse mental and physical developmental abnormalities have been observed. In additional human cohorts where exposure could be considered as environmental or background, more subtle effects, including lower birth weights, alterations in thyroid hormones and lymphocyte subpopulations and detriments in neurological development, have been consistently seen. In most instances, negative associations were made between in utero exposure to contaminants compared with lactational. Although the observed neurodevelopmental deficits have been described as subtle, there could be unknown consequences related to future intellectual functionality. Current regulatory efforts should focus on identification and control of environment and food chain contamination as in utero exposure is a direct consequence of the accumulated maternal body burdens.

Accidents↗

Human health implications of environmental contaminants in Arctic Canada: a review.

This paper assesses the impact on human health of exposure to current levels of environmental contaminants in the Canadian Arctic, and identifies the data gaps that need to be filled by future human health research and monitoring. The concept of health in indigenous groups of the Arctic includes social, cultural, and spiritual dimensions. The harvesting, sharing and consumption of traditional foods are an integral component to good health among Aboriginal people influencing both physical health and social well-being. Traditional foods are also an economic necessity in many communities. Consequently, the contamination of country food raises problems which go far beyond the usual confines of public health and cannot be resolved by health advisories or food substitutions alone. The primary exposure pathway for the contaminants considered in this paper is through the traditional northern diet. For the Inuit, the OCs of primary concern at this time from the point of view of exposure are chlordane, toxaphene, and PCBs. Exposures are higher in the eastern than in the western region of the North. For Dene/Metis, exposure to OCs is in general below a level of concern. However, estimated intake of chlordane and toxaphene has been found to be elevated for certain groups and is a cause for concern if exposures are elevated on a regular basis. The developing foetus and breast-fed infant are likely to be more sensitive to the effects of OCs and metals than individual adults and are the age groups at greatest risk in the Arctic. Extensive sampling of human tissues in the Canadian north indicate that a significant proportion of Dene, Cree and Inuit had mean maternal hair mercury levels within the 5% risk-range proposed by the WHO for neonatal neurological damage. Based on current levels, lead does not appear to pose a health threat while cadmium is likely only a major risk factor for heavy smokers or consumers of large amounts of organ meats. Consumers of traditional foods are exposed to an approximately seven-fold higher radiation dose than non-consumers of traditional foods due predominantly to the bioaccumulation of natural radionuclides in the food chain. Risk determination for contaminants in country food involves a consideration of the type and amounts of food consumed and the sociocultural, nutritional, economic, and spiritual benefits associated with country foods. Risk management options that minimize the extent to which nutritional and sociocultural aspects of Aboriginal societies are compromised must always be considered.

Adult↗

The temporal relation of adherence and alliance to symptom change in cognitive therapy for depression.

This study attempted to replicate an earlier study (R. J. DeRubeis & M. Feeley, 1990) of the prediction of symptom change from process variables in cognitive therapy for depressed outpatients. Measures of in-session therapist behavior and therapist-patient interactions were correlated with prior and subsequent symptom change. One of the positive findings was confirmed, but the other received only marginal support. A "concrete" subset of theory-specified therapist actions, measured early in treatment, predicted subsequent change in depression. The therapeutic alliance was predicted by prior symptom change in 1 of the 2 later assessments, but only at a trend level. Several negative findings were similar to those obtained in the earlier study. Specifically, the alliance, an "abstract" subset of theory-specified therapist actions, and facilitative conditions did not predict subsequent change. Implications for causal inferences in psychotherapy process research are discussed.

Adult↗

Risk factors for predicting surgical salvage of sternal wound-healing complications.

A retrospective study was performed to determine whether clinical factors can predict which complicated poststernotomy wounds can be managed successfully by debridement and reclosure, and which wounds require a muscle flap for healing. Between January 1990 and December 1996, 3,435 median sternotomies were performed at Indiana University Medical Center and affiliated hospitals. A total of 91 patients (2.6%) were reoperated for sternal wound-healing complications. Seventy-six patients (83.5%) underwent debridement and rewiring, and 15 patients (16.5%) underwent primary flap coverage. Of the 76 patients who underwent initial rewiring, 45 (59%) healed and 31 (41%) required additional operative procedures. Of the 31 rewiring failures, 26 patients (84%) were healed with muscle flaps and 4 patients (13%) were managed with a second successful rewiring. The following clinical factors were correlated with operative procedure and outcome: history of smoking, chronic obstructive pulmonary disease, steroid use, previous sternotomy, age, diabetes, harvest of the left or right internal mammary artery (IMA), emergency operation, operation time, pump time, cross-clamp time, ischemic time, coronary artery bypass grafting alone versus combined with a valve replacement, positive wound cultures, positive blood cultures, elevated white blood cell count, and fever. When comparing patients with successful rewiring with those who had a failed rewiring, positive wound and blood cultures were significant risk factors (p < 0.05) on univariate analysis. Presence of a positive wound culture was significant on multivariate analysis. When comparing risk factors in patients who were rewired successfully versus all patients who had muscle flap coverage, the presence of a positive blood culture was significant on both univariate and multivariate analyses. We conclude patients most likely to fail rewiring and to require muscle flap closure are those with infected wounds, positive blood cultures, and possibly left IMA bypasses.

Adult↗

Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife.

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties.

Animals↗

Subchronic toxicity of 2,2',3,3',4,4'-hexachlorobiphenyl in rats.

The subchronic toxicity of 2,2',3,3',4,4'-hexachlorobiphenyl (PCB 128) was investigated in rats following dietary exposure at 0, 0.05, 0.5, 5, or 50 ppm for 13 wk. The growth rate was not affected by treatment and no apparent clinical signs of toxicity were observed. There was a significant increase in liver weight in the 50 ppm females. The liver ethoxyresorufin deethylase (EROD) activity was increased by five- and fourfold in the highest dose males and females, respectively, while aminopyrine demethylase (ADPM) activity was significantly increased only in the highest dose females. Liver vitamin A was significantly reduced in the highest dose females. No other biochemical or hematological effects were observed. Treatment-related histopathological changes were seen in the thyroid and liver, and to a lesser extent in the bone marrow and thymus. Residue data showed a dose-dependent accumulation of PCB 128 in the following tissues: fat, liver, kidney, brain, spleen, and serum, with the highest concentration being found in fat followed by liver and kidney. Based on these data, the no-observable-adverse-effect level of PCB 128 was judged to be 0.5 ppm in diet or 42 micrograms/kg body weight.

Adipose Tissue↗

Toxicity of 2,4,4'-trichlorobiphenyl in rats following 90-day dietary exposure.

The toxicity of 2,4,4'-trichlorobiphenyl (PCB 28) was investigated in rats after a 90-d dietary exposure. Groups of 10 male and 10 female weanling Sprague-Dawley rats were administered PCB 28 in the diet at 0, 0.05, 0.50, 5.0, or 50.0 ppm for 13 wk. Growth rate and food consumption were not affected by treatment, and no clinical signs of toxicity were observed. Mottled liver was noted in both control and PCB-treated males, but was found with increased incidence in the highest treatment group. Increased urinary ascorbic acid and hepatic microsomal ethoxyresorufin O-deethylase activity were observed in the 50.0 ppm group of both sexes. The vitamin A content in liver, lung, and kidney was not significantly affected by treatment. Analysis of brain biogenic amines showed a decreased dopamine concentration in the substantia nigra region of female rats receiving 0.5 ppm PCB 28 and higher doses. Female rats appeared to be more sensitive than males to the neurochemical effects of PCB 28. Dose-dependent histologic changes were observed in the thyroid and liver, with biologically significant changes occurring at 5.0 ppm and above. Based on these data, the no observable-adverse-effect level (NOAEL) for this PCB congener was considered to be 0.5 ppm in diet or 36 micrograms/kg body weight/d.

Administration, Oral↗

Subchronic toxicity of 3,3',4,4',5-pentachlorobiphenyl in the rat. I. Clinical, biochemical, hematological, and histopathological changes.

The systemic toxicity of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) following subchronic dietary exposure was investigated in Sprague-Dawley rats. PCB 126 was administered to rats of both sexes at concentrations of 0.1, 1.0, 10, or 100 ppb in their diet for 13 weeks. Another group of rats received a loading dose of 5 micrograms PCB/kg body wt at the start of the feeding period followed by exposure to 10 ppb PCB diet for the same period of time as the other groups. Growth suppression and decreased food consumption were observed in the highest dose groups of both sexes. Increased organ/body weight ratios for the liver occurred in the 10 and 100 ppb groups of both sexes. Rats of both sexes exposed to the highest dose of the PCB also exhibited increased relative kidney, spleen, and brain weights. Hematological and most serum biochemical changes were confined to the 100 ppb groups. These included elevated alkaline phosphatase, bilirubin, cholesterol, and aspartate aminotransferase, and decreased serum glucose, hemoglobin, erythrocytes, hematocrit, and platelets. A dose-dependent increase in liver ethoxyresorufin-O-deethylase activity was observed in rats of both sexes starting at 0.1 ppb. A dose-dependent increase in liver uroporphyrin levels was observed in both sexes and significant changes occurred in the female rats at 1.0 ppb and higher dose groups. Decreased liver vitamin A was observed in the 10 ppb group and higher in both sexes. Kidney vitamin A was elevated in the 100 ppb group. No statistically significant changes were noted in concentrations of brain biogenic amines. PCB 126 residues were 10-fold higher in liver than in fat. Treatment-related histopathological changes were observed in the thymus, thyroid, bone marrow, and liver of rats exposed to the 10 ppb diet, but increased frequency of mild changes was observed in most of these tissues at the 1.0 ppb level. Based on the above data, the no adverse effect level was judged to be 0.1 ppb in the diet or 0.01 micrograms/kg body wt/day.

Animals↗

Role of xanthine oxidase inhibition in survival from hemorrhagic shock.

The irreversible loss of adenine nucleotides and the formation of free radicals have both been suggested as causes of irreversibility following prolonged hemorrhagic shock. This study was performed to assess the effect of xanthine oxidase inhibition (allopurinol 50 mg/kg/day), free radical scavenging (superoxide dismutase 15,000 u/kg, catalase 15,000 u/kg, dimethylsulfoxide 20 mg/kg, and alpha tocopherol 100 mg/kg/day) or both, on the 24-hr survival of dogs subjected to irreversible haemorrhagic shock. Twenty anesthetized dogs were bled to a mean arterial pressure of 30 mm Hg for 4 hr. The dogs were allocated to a control, an allopurinol pretreated, a free radical scavenger, or a combined treatment group. Both groups pretreated with allopurinol had significantly improved survival (P < 0.05) over that seen in the control group, but the free radical scavenger treated group was not significantly different from the control group. This study demonstrates the beneficial effect of xanthine oxidase inhibition on survival, and suggests that it may be due to preservation of adenine nucleotides rather than prevention of free radical formation.

Allopurinol↗

Staff distress among haemophilia nurses.

To investigate the severity, sources, and means used to cope with the distress experienced by haemophilia nurses as a result of the widespread infection with Human Immunodeficiency Virus among haemophiliacs, we collected anonymous questionnaire data from all nurses in the Haemophilia Nursing Network Directory, compiled by the National Haemophilia Foundation in June, 1990. Questionnaires were returned by 136 of the 181 (75%) nurses in the sample. Over 50% of the sample gave distress responses to 15 of 44 statements. Areas associated with the greatest distress were: (1) Failure of patients to take steps to prevent transmission of HIV; (2) Fear of getting infected, and (3) the repeated loss experienced as patients died from infection. Nurses working with haemophiliacs for 11-15 years were particularly vulnerable to feelings of guilt for having participated in the treatment that resulted in HIV infection. Fear of contagion and distress from patient deaths were mutually exclusive ways of reacting to HIV in haemophiliacs. Looking for a new job was related to all major sources of distress. Interaction with peers was perceived as being the most useful source of emotional support.

Acquired Immunodeficiency Syndrome↗

Hyperthermic potentiation of BCNU toxicity in BCNU-resistant human glioma cells.

Experimental evidence indicating potentiation of the cytotoxic effect of drugs at high temperatures suggests that the utilization of drug-heat combinations for gliomas of the brain might be therapeutically useful. Hyperthermia may increase the cytotoxicity of a particular drug in areas of low drug concentration/time and in cell populations resistant to the drug. We report in vitro experiments with a BCNU resistant, U-373MG, and a BCNU sensitive, U-87MG, human derived glioma cell lines under hyperthermic conditions. Temperatures equal or above 42 degrees C potentiate BCNU cell kill in both lines. The thermo-sensitizer lidocaine increases thermal cell kill but only minimally with concentrations corresponding to therapeutic plasma lidocaine levels. Within our experimental conditions, the best strategy to overcome BCNU resistance involved a combination of heat, BCNU and cis-DDP. BCNU resistant cells have no cross resistance to cis-DDP and the combination of BCNU and cis-DDP is synergistic. At modest hyperthermic conditions (42 degrees C) 99.4% BCNU resistant cells are killed by a combination of BCNU and cis-DDP at drug concentrations identical to plasma concentrations after standard IV doses. Clinical protocols using heat and drug may need to incorporate two or more drugs for optimal effects.

Carmustine↗

Upper limb embolus: a timely diagnosis.

In a ten year period, 36 patients were treated surgically for embolic occlusion of upper limb vessels. The sources of embolus were cardiac (58%), peripheral aneurysm (22%) and unknown (20%). Brachial embolectomy was performed in all cases. Six out of eight peripheral aneurysms were resected. A patency rate of 94% was achieved at five years. Hospital mortality and morbidity rates were 3% and 10%, respectively. One patient died of a myocardial infarct one week postoperatively. Three patients suffered ischemic contracture or amputation; all three presented after 36 hours. We conclude that upper limb emboli are usually easy to recognize and treat. Prompt surgery (less than 24 hours) produces the most satisfactory results. Late presentation or delay in treatment can result in limb loss.

Acute Disease↗

Inhibitors of repair of potentially lethal damage and DNA polymerases also influence the recovery of potentially neoplastic transforming damage in C3H10T-1/2 cells.

The effects of aphidicolin and beta Ara A on radiation sensitivity were evaluated in terms of cell killing, recovery, and neoplastic transformation in the C3H10T-1/2 cell system. When cells were held in plateau phase, recovery of potentially lethal damage (PLD) and potentially transforming damage (PTD) occurred. The addition of beta Ara A resulted in reduced PLD recovery for both the survival and neoplastic transformation end points. The addition of aphidicolin did not affect recovery of PLD or PTD. These data show that the inhibition of polymerase alpha by aphidicolin does not affect recovery of damage leading to cell death or neoplastic transformation. However, the inhibition of both polymerase alpha and beta by beta Ara A resulted in inhibition of recovery of damage leading to both cell death and neoplastic transformation. These data indicated that polymerase beta may be involved in both PLD and PTD recovery.

Animals↗

Congenital arteriovenous malformation of the scalp with high output cardiac failure: a case report.

A 19-year-old man was diagnosed with a rapidly enlarging arteriovenous malformation of the scalp and a mild degree of cardiomegaly. Operation to excise the large fistula took place under general anesthesia. Both external carotid arteries and their branches were controlled to prevent intraoperative hemorrhage, and dissection took place down to the periosteum. A split skin graft from the thigh was applied to the scalp defect. The patient recovered well with no further evidence of dyspnea or high output cardiac failure.

Adult↗