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Biomedical subjects

J Nolan

Publications and source records attributed to J Nolan.

At least 127 records · Page 7Linked to original sources
PubMed1991

Pseudo preexcitation syndrome.

During the course of investigation for palpitations, a 62-year-old man underwent exercise testing using a MARQUETTE CASE 12 computerized exercise testing system. By stage III of the modified Bruce protocol, the computer-generated electrocardiogram appeared to show the development of exercise-induced preexcitation. Closer examination of the raw unfiltered data showed this to be a computer-generated artifact rather than true preexcitation. This artifact arose due to inherent limitations common to all computerized exercise testing systems and emphasizes the need to always review raw data, even when a seemingly clear-cut abnormality is present on a computer-averaged electrocardiogram.

Artifacts↗
PubMed1991

Oral (po) dosing with RSU 1069 or RB 6145 maintains their potency as hypoxic cell radiosensitizers and cytotoxins but reduces systemic toxicity compared with parenteral (ip) administration in mice.

RB 6145 is a pro-drug of the hypoxic cell radiosensitizer RSU 1069 with reduced systemic toxicity. The maximum tolerated dose (MTD) of RSU 1069 for C3H/He mice was 80 mg/kg (0.38 mmol/kg) ip but 320 mg/kg (1.5 mmol/kg) following po administration. The MTD values of RB 6145 were 350 mg/kg (0.94 mmol/kg) ip and 1 g/kg (2.67 mmol/kg) po. Toxicity of RSU 1069 toward bone marrow stem cells was also less after po administration than after ip administration; 0.1 mmol/kg ip RSU 1069 and 0.38 mmol/kg po RSU 1069 both reduced the surviving fraction of clonogenic CFU-A cells by 50%. Oral administration of RSU 1069 resulted in lower spermatogenic toxicity. No loss of intestinal crypts was detected after ip or po administration of RSU 1069. Some nephrotoxicity was observed in half of the mice given the highest po dose of 1.5 mmol/kg of RSU 1069; this was not observed following the highest ip dose of drug. For RSU 1069 and RB 6145, administered by either route, the maximum hypoxic cell radiosensitization in murine KHT sarcomas, occurred when the drugs were given 45-60 min before 10 Gy of X rays. The degree of radiosensitization produced by a particular dose of either compound was largely independent of the route of administration. Preliminary pharmacokinetic studies, using 3H-RSU 1069, suggested that anti-tumor efficacy correlated with peak blood level of label and concentration in the tumor at the time of irradiation, which were not reduced by po compared with ip administration. Normal tissue toxicity tended to correlate with total exposure over time, which was reduced approximately two-fold by po administration. Oral administration of RSU 1069 or RB 6145, as well as being convenient, may give therapeutic benefit since dose-limiting toxicity in mice was reduced compared with parenteral administration, whereas radiosensitizing activity was less affected.

Administration, Oral↗
PubMed1990

Air quality in the vicinity of urban roads.

Motor vehicle emissions are a major source of CO, NOx and lead particulate concentrations to urban air quality. London urban Boroughs with high traffic densities are therefore a particular cause for concern. The air quality was monitored at an urban background site in the London Borough of Haringey for 2-years. The results of this study are assessed and their effect on human health is considered in the light of EC Directives and WHO guidelines. A desk top modelling technique based on Gaussian diffusion theory was used to predict the CO levels found at the background site. All predicted levels had a accuracy of better than 30%.

Air Pollution↗
PubMed1990

Heavy metal levels in the near vicinity to roads in a north London Borough.

The ingestion and inhalation of heavy metals through soil, surface dust, air and food contamination may have a detrimental effect on human health. Metal levels have been measured in a Local Authority in London, UK and are discussed where possible in relation to health risk and relevant guidelines.

Child↗
PubMed1990

Tissue distribution of 14C- and 3H-labelled misonidazole in the tumor-bearing mouse.

The retention of labelled misonidazole (MISO) was measured in a range of normal tissues in the mouse 24 hr after the intravenous injection of [14C]MISO (ring labelled) and [3H]-MISO (side-arm labelled). For [14C]MISO the 24 hr tissue retention, in order of the highest to the lowest levels (excluding pathways of excretion), was esophageal epithelium, liver, foot pad, eyelid, lung, subcutaneous lung tumor (A110), esophageal wall, uterus, eye ball, blood, salivary gland, spleen, voluntary muscle, pancreas, inguinal fat. It was assumed that the 14C represented MISO metabolite(s) bound to macromolecules. An approximately similar pattern was observed for [3H]MISO, but a higher percentage of the injected activity per gram of tissue was retained, probably due to the presence of tritiated water in the tissues. It has generally been assumed that significant levels of MISO binding are restricted to hypoxic tissues, for example tumors, but the present results show that significant levels of binding can also occur in apparently normoxic tissues. The explanation is put forward that this binding may be due to local high levels of nitroreductase capacity.

Adenocarcinoma↗
PubMed1990

NAD(P)H nitroblue tetrazolium reductase levels in apparently normoxic tissues: a histochemical study correlating enzyme activity with binding of radiolabelled misonidazole.

Hack and Helmy's method for the histochemical identification of NAD(P)H nitroblue tetrazolium reductase activity was employed to pinpoint reductase activity in certain cells in the mouse. High activity was observed in the following: lower airway epithelium, liver (centrilobular zone), eyelid (meibomian and sebaceous glands), vulval gland and parotid gland (striated cells of intralobular ducts). All of these cells had previously been identified as sites of binding of the reactive metabolites formed from the enzymic reduction of misonidazole (MISO) (Cobb et al., 1989). It had previously been thought that MISO binding would only take place in significant amounts in hypoxic tissues (tumour and possibly liver) since in normoxic tissues oxygen should reverse the initial one electron enzymic reduction, thus preventing progressive reduction to reactive species. We suggest that the very high levels of reductase in the above listed, probably normoxic, tissues contribute significantly to the accumulation of bound reactive MISO metabolite(s).

Animals↗
PubMed1990

Distribution of pimonidazole and RSU 1069 in tumour and normal tissues.

The tritium-labelled analogues of pimonidazole and RSU 1069 were injected into mice bearing the KHT murine sarcoma which has a hypoxic cell fraction of approximately 10%. The distribution of activity at 24 h was recorded using autoradiography and measurement of tissue activity. Autoradiographs with both drugs showed high activity in particular cells within tumour, eye (melanin-associated cells), eyelid (Meibomian gland), liver (centrilobular area), skin (sebaceous gland and melanin), stomach (squamous area), footpad, oesophagus, labial gland, Zymbal's gland, preputial gland, parotid gland (intralobular ducts) and airway epithelium. These tissues had previously been identified as sites of binding of misonidazole. The measurement of total tissue radioactivity showed significantly higher activity in liver, eyelid (Meibomian gland), oesophageal lining, kidney and labial gland than was found in the tumour.

Animals↗
PubMed1990

Diet in the epidemiology of gastric cancer.

We examined the nutritional epidemiology of gastric cancer in 293 cases and neighborhood-, age-, and sex-matched controls in communities throughout the counties of Niagara, Monroe, and Erie in western New York. The interview was highly detailed, requiring two and one-half hours to complete; it attempted to provide an estimate of total calories ingested as well as of macro- and micronutrients and behaviors that could affect alimentary exposures, such as the use of refrigeration. We found that risk was enhanced by sodium, fat, and retinol. Substantial reductions in risk were associated with ingestion of carotene, especially raw vegetables (including celery, cucumbers, carrots, green peppers, tomatoes, and onions), as well as with increased use of low-temperature food storage. Both refrigeration and carotene could inhibit oxidation products that could act as carcinogens in the stomach.

Adult↗
PubMed1990

Nutritional epidemiology of cancer of the esophagus.

This study of 178 cases of cancer of the esophagus from three counties in western New York, as compared with sex- and age-matched neighborhood controls in 1975-1986, replicated some earlier findings, particularly with regard to the increased risks associated with use of cigarettes and alcohol. The concentration of alcohol in an alcoholic beverage apparently did not affect risk: Beer carried a substantial risk, whereas less-dilute forms of alcohol carried no risk. These findings also suggest that the risk of cancer of the esophagus increases with ingestion of foods containing retinol but not carotene. Although increased risks were found to be associated with increases in total calories and fat ingested, as well as calcium, they appeared to be confounded with the risk associated with retinol, as distinct from carotene. Inasmuch as a difference in risk associated with retinol and carotene has been shown in a few previous inquiries dealing with esophageal cancer and cancer at other sites, a need for further investigations distinguishing risks associated with the two compounds is apparent.

Beer↗
PubMed1990

Acaricide resistance in single and multi-host ticks and strategies for control.

The majority of reports, concerning resistance in multi-host ticks, continue to be confined to the cyclodiene group and lindane, with sparse references to resistance affecting the organophosphorus acaricides. In contrast, the resistance picture in Boophilus spp., particularly in relation to B. microplus in Australia, continues to degenerate. Recent reports, documenting the emergence of a complex of pyrethroid resistant strains in the latter species, are the cause of considerable current concern, due to the lack of a suitable, commercially available, replacement group. These developments reinforce the need for a close examination of the strategies recommended for the management of acaricide resistance, particularly for Boophilus spp. The choice of options to select, in circumstances following the detection of resistance to an acaricide, is limited to those aimed at preserving the use of the affected chemical, or selection of an effective alternative, either from within the same class, or from a new acaricide group. Success of the former options, including tactics such as increased concentration or eradication of resistant alleles, and the rational choice of alternative acaricides for use in localized areas where necessary, are critically dependent on early detection of a newly emerged resistance mechanism, its localization, and an understanding of its spectrum of effect. Avermectins and acarine growth regulators show promise as potential future tick control agents. However, the dearth of new chemistry in this area stresses the importance of developing optimal strategies to extend the effective life of these and currently available compounds, in areas where they remain effective.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Posterior mediastinal teratoma involving the esophagus.

Intrathoracic teratomas are difficult to diagnose on chest radiographs if they are noncalcified and located in an atypical site. We report an unusual case of posterior mediastinal teratoma that involved the esophageal wall. Features noted on computed tomography (CT) of the chest and barium examination of the esophagus are herein presented.

Diagnosis, Differential↗
PubMed1989

Leiomyoma of spermatic cord with unusual features.

We describe a case of a patient with osseous metaplasia and chronic inflammatory changes in a leiomyoma of the spermatic cord, as well as a lipoma of the cord with similar changes. The differential diagnosis and possible etiology of these findings are presented.

Aged↗
PubMed1989

Autoradiographic study of tritium-labeled misonidazole in the mouse.

The localization of tritiated misonidazole metabolites in a number of normal tissues in the mouse is reported from autoradiography. The labeled misonidazole was injected at 750 or 75 mg/kg body weight (Rel. Sp. Act. 74 and 740 MBq/mg respectively). The grain count ratio, parenchyma:stroma, for selected tissues was: liver (centrilobular zone) 13; meibomian gland (acini) 68, (duct) 116; esophagus (keratinized layer) 61; enamel organ 17. It is concluded that there are a number of tissues which will accumulate MISO metabolites although they may not all be hypoxic.

Animals↗
PubMed1989

Microscopic distribution of misonidazole in mouse tissues.

Mice were injected with tritiated misonidazole (750 mg/kg-1), killed after 24h and the excised tissues prepared for autoradiography (ARG) to identify sites of accumulation. The previously reported high grain count associated with bound misonidazole metabolite(s) was observed in the liver. The ratio of grain count in the emulsion above the centrilobular hepatocytes to the count over connective tissue (stroma) was 12. A higher count ratio for 'target' cells to stroma was observed in the following cells/tissues: meibomian gland (ducts 110, acini 65), oesophagus (keratinised layer 60), incisor (enamel organ 17), nasal septum (subepithelial glands 13). For some of these tissues the explanation might appear to lie with localised hypoxia, but for others which were probably normoxic there is as yet no obvious reason for these findings.

Animals↗
PubMed1989

Synthetic pyrethroid resistance in field samples in the cattle tick (Boophilus microplus).

First evidence of resistance to synthetic pyrethroids in the cattle tick in Australia, other than the pre-existing cross-resistance in DDT-resistant ticks, has emerged. Three new strains have been investigated and characterised. The first, detected in central Queensland, showed increased ability to detoxify pyrethroids resulting in a marginal loss of efficacy of all pyrethroid tickicides tested, except flumethrin. Subsequently two more strains have been detected, with serious implications for chemical tick control. The first, from southern Queensland, has a high level of specific resistance to flumethrin. The second, from central Queensland, has a broad spectrum resistance encompassing all pyrethroids currently in use. The toxicology and biochemistry of these new resistant strains have been investigated and alternative tickicides evaluated. The significance of these latest developments is discussed.

Animals↗
PubMed1989

Zoladex versus danazol in the treatment of pelvic endometriosis: effects on plasma lipid risk factors.

Plasma lipid risk markers for coronary heart disease (CHD) are influenced by sex steroid concentrations. Therapies that alter sex hormone levels have the potential to affect CHD risk. Zoladex had no effect on plasma lipids, but increased high density lipoprotein (HDL) subfraction 3, a lipoprotein of uncertain clinical significance. Danazol increased low density lipoprotein and decreased HDL concentrations to give a lipid profile associated with increased risk of CHD.

Buserelin↗
PubMed1988

Potentiation of the anti-tumour effect of melphalan by the vasoactive agent, hydralazine.

The vaso-active drug hydralazine causes a considerable increase in the cytotoxic effect of melphalan towards the KHT tumour in mice. The enhancement in response, measured as the concentration of melphalan required to achieve a given tumour response, is 3.0 and 2.35 when determined using the regrowth delay assay and the technique for determining surviving fraction in vitro following treatment in vivo respectively. In contrast, measurement of systemic toxicity shows that the addition of hydralazine only causes a small increase (ER = 1.15) in melphalan damage. This suggests that the drug combination may have some therapeutic benefit. The tumour specificity for the action of hydralazine is supported by the finding that binding of 3H-misonidazole is increased in tumours but not in other tissues when mice are treated with hydralazine. Increased binding of labelled misonidazole is associated with an increase in the level and duration of hypoxia, which will occur as a consequence of changes in tumour blood flow brought about by hydralazine. However, hypoxia per se is not responsible for the enhanced effect of melphalan, since the agent BW12C, which also induces substantial tumour hypoxia as a result of changing the O2 affinity of haemoglobin, has no effect on melphalan tumour cytotoxicity.

Animals↗