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Biomedical subjects

R McNally

Publications and source records attributed to R McNally.

17 recordsLinked to original sources
PubMed2003

Parental smoking and childhood cancer: results from the United Kingdom Childhood Cancer Study.

There are strong a priori reasons for considering parental smoking behaviour as a risk factor for childhood cancer but case - control studies have found relative risks of mostly only just above one. To investigate this further, self-reported smoking habits in parents of 3838 children with cancer and 7629 control children included in the United Kingdom Childhood Cancer Study (UKCCS) were analysed. Separate analyses were performed for four major groups (leukaemia, lymphoma, central nervous system tumours and other solid tumours) and more detailed diagnostic subgroups by logistic regression. In the four major groups, after adjustment for parental age and deprivation there were nonsignificant trends of increasing risk with number of cigarettes smoked for paternal preconception smoking and nonsignificant trends of decreasing risk for maternal preconception smoking (all P-values for trend >0.05). Among the diagnostic subgroups, a statistically significant increased risk of developing hepatoblastoma was found in children whose mothers smoked preconceptionally (OR=2.68, P=0.02) and strongest (relative to neither parent smoking) for both parents smoking (OR=4.74, P=0.003). This could be a chance result arising from multiple subgroup analysis. Statistically significant negative trends were found for maternal smoking during pregnancy for all diagnoses together (P<0.001) and for most individual groups, but there was evidence of under-reporting of smoking by case mothers. In conclusion, the UKCCS does not provide significant evidence that parental smoking is a risk factor for any of the major groups of childhood cancers.

Adolescent↗
PubMed2001

Preliminary quantitative investigation of postmortem adipocere formation.

The accurate determination of postmortem interval (PMI) using the formation of adipocere presents a significant challenge to forensic scientists interested in determining the time of death. Several attempts have been made to determine the time since the occurrence of death. However, up to date, this has been difficult because previous approaches have been mainly qualitative, focusing on the later stages of degradation processes. This work presents preliminary results of an experimental model of postmortem adipocere formation using liquid chromatography. Three pig cadavers were submerged in distilled water, chlorinated water, and saline water. Fresh specimens resulting from the degradation in the subcutaneous fat were obtained from the pigs at two-week intervals for a period of ten weeks, and were subjected to chromatographic analysis. By correlating the ratio of the disappearance of hydrolyzed fatty acids with the formation of hydroxystearic and oxostearic acids after death, a simple, quantitative analytical method was developed for the determination of PMI. Experimental observation of the chemistry of adipocere formation indicated that adipocere can be formed only a few hours after an incidence of death and this continues until the saturation of oleic acid degradation after several weeks. Different time courses were obtained for cadavers immersed in distilled, chlorinated, and saline water, respectively. This work has not in any way solved the time since death problem. But it may be an approach to the problem that has not been adequately explored.

Animals↗
PubMed2000

Adult psychosocial outcomes in long-term survivors of acute lymphoblastic leukaemia and Wilms' tumour: a controlled study.

BACKGROUND: Variability in methods and deficits in design have contributed to conflicting findings about adult psychosocial functioning after childhood cancer. We did a controlled study of psychosocial outcomes in adult survivors of childhood acute lymphoblastic leukaemia (ALL) and Wilms' tumour to address previous methods limitations. METHODS: We assessed 102 survivors of childhood ALL and Wilms' tumour, who had been free from relapse for 5 years and were aged 19-30 years, and 102 unrelated healthy controls. We used standard measures of adult psychiatric disorder, interpersonal and social-role performance, and intellectual ability to assess past and current functioning. FINDINGS: Cancer survivors had no increased rates of psychiatric disorder. Mean scores of cancer survivors were significantly higher (indicating poorer functioning) than those of controls for love/sex relationships (mean difference 0.87 [95% CI 0.53-1.22]), friendships (0.37 [0.07-0.67]), non-specific social contacts (0.40 [0.20-0.60]), and day-to-day coping (0.35 [0.14-0.57]). Cancer survivors were more likely than controls to have a combination of deficits in love/sex relationships and friendships (ALL survivors odds ratio 10.83 [95% CI 3.87-30.82], Wilms' tumour survivors 4.85 [1.43-16.47]), which was associated with more recent treatment (p=0.005). Poor coping was associated with lower intellectual ability scores (p=0.018). INTERPRETATION: Childhood ALL and Wilms' tumour have long-term effects on interpersonal functioning and coping, probably mediated by different mechanisms. Prospective studies with each of these tumour groups are needed with similar adolescent and adult outcome measures.

Adaptation, Psychological↗
PubMed1999

IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice.

Macrophages derived from IFN-regulatory factor-1 (IRF-1) and IRF-2 knockout (-/-) and wild-type (+/+) mice were utilized to examine the role of these transcription factors in the regulation of IL-12 mRNA and protein expression. Induction of IL-12 p40 mRNA by LPS was markedly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages. In contrast, IRF-1(-/-), but not IRF-2(-/-), macrophages exhibited impaired LPS-induced IL-12 p35 mRNA expression. The ability of IFN-gamma to augment LPS-induced IL-12 p40 mRNA further when both stimuli were present simultaneously was significantly diminished in both IRF-1(-/-) and IRF-2(-/-) macrophages, with the most profound impairment observed for IRF-1(-/-) macrophages. Reductions in IL-12 mRNA expression after stimulation with LPS or LPS plus IFN-gamma were accompanied by substantial reductions in IL-12 p40 and IL-12 p70 protein in both IRF-1(-/-) and IRF-2(-/-) macrophages. Priming IRF-1(-/-) and IRF-2(-/-) macrophages with IFN-gamma for 24 h before LPS treatment partially restored impaired IL-12 mRNA and protein production in both IRF-1(-/-) and IRF-2(-/-) macrophages. Depressed IL-12 levels were paralleled by significant reductions in IFN-gamma mRNA expression in IRF-1(-/-) and IRF-2(-/-) macrophages. These results indicate that both IRF-1 and IRF-2 are critical transcription factors in the regulation of macrophage IL-12 and consequently IFN-gamma production.

Animals↗
PubMed1999

The rise in incidence of lymphomas in Europe 1985-1992.

A collaborative study was carried out of the descriptive epidemiology of the lymphomas from seven countries across Europe in the period 1985-1992. Careful attention was paid to sources of information and the data quality in close collaboration with expert histopathologists. The data were classified as non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD). An attempt was made to put the data into a modified version of the Revised European American Lymphoma (REAL) classification. We observed an overall rise in total NHL throughout the time period in all European countries but no such trend in HD. The increase in NHL overall being 4.2% per annum, representing an increase of 4.8% in males and 3.4% in females per annum, was only marked in middle and old age. Such increases were observed in all participating areas except in Burgundy. Different countries, however, have different base rates, the rates being highest in Scandinavia and the Netherlands. The analysis by subcategory classification suggested that the increase in NHL was confined to the follicle centre cell type, extranodal B-cell, nodal T-cell and nodal lymphomas not otherwise specified, categories. These new observations present a picture of real increase in case incidence with no obvious explanation. The increases in NHL do not appear to be due solely to better diagnoses. Pending other explanations or refutation, these present a compelling picture of an inexorable rise in incidence of this disease.

Adolescent↗
PubMed1998

The changing incidence of lymphoproliferative disorders in Yorkshire.

Secular trends in the incidence of lymphoproliferative disorders on North and West Yorkshire and Humberside from 1985 to 94 were studied and changes in incidence by tumour subtype were analysed. Population-based data on the incidence of lymphoproliferative disorders were obtained from a specialist registry with a high level of ascertainment. Cases of chronic lymphocytic leukaemia and plasma cell myeloma were excluded and the remaining cases classified as Hodgkin's disease and non-Hodgkin's lymphoma (NHL). NHL were subdivided by site of origin and immunophenotype. Nodal B-cell lymphomas were further classified as diffuse large B-cell lymphoma, follicle centre lymphoma, mantle cell lymphoma and miscellaneous. During the study period there was a significant increase in total lymphoproliferative disorders with an average change of 2.5% per annum equivalent to 0.84/10,0000. Most of this increase was due to an increasing incidence of extranodal B-cell lymphomas and peripheral T-cell lymphomas. A numerically small but significant increase in diffuse large B-cell lymphomas was seen. There was no significant increase in other subtypes. The increased incidence of lymphomas in the area studied is mainly due to changes in two specific subgroups. There are several reasons why changes in extranodal B-cell lymphoma and peripheral T-cell lymphoma may have been particularly affected by changing diagnostic practices. Epidemiological studies of particular subtypes of lymphoproliferative disorder facilitate the identification of environmental factors involved in the pathogenesis of these tumours.

Adolescent↗
PubMed1998

Incidence and time trends in Hodgkin's disease: from parts of the United Kingdom (1984-1993).

Over 3,000 cases of Hodgkin's Disease diagnosed between 1984-93 were used to examine incidence and time trends. These data are part of the Leukaemia Research Fund's specialist Data Collection Study, which is the only large, population-based data set of its type in Europe. The age specific incidence curves showed different patterns for nodular sclerosis contrasted with all other subtypes combined (non-nodular sclerosis). For nodular sclerosis, there was a female excess for young adults, while for non-nodular sclerosis a gradual rise in incidence with age in both sexes was observed. Incidence varied over time, showing a complex pattern with a decreasing trend in males in all Rye-subtypes and no significant change among females diagnosed with nodular sclerosis. These complex patterns of change are different from those seen in other countries. It is concluded that the results provide clear evidence of the heterogeneity of Hodgkin's disease between the sexes and between subtypes, which should be taken into account in future studies.

Adolescent↗
PubMed1997

Regulation of inducible nitric oxide synthase messenger RNA expression and nitric oxide production by lipopolysaccharide in vivo: the roles of macrophages, endogenous IFN-gamma, and TNF receptor-1-mediated signaling.

To evaluate potential roles for macrophages, IFN-gamma, and TNF receptor 1 (TNFR1) in the regulation of LPS-induced inducible nitric oxide synthase (iNOS) mRNA expression, we used a model of macrophage depletion as well as IFN-gamma (GKO) and TNFR1 (TNFR1 -/-) knockout mice. LPS-induced iNOS mRNA in spleen was ablated in both macrophage-depleted and GKO mice. In livers of macrophage-depleted mice, LPS-induced iNOS mRNA was reduced by 55 to 85%, with the most profound reductions detected 6 and 8 h after LPS injection. In GKO mice, peak iNOS mRNA expression in liver (3 h) was unaffected by the loss of endogenous IFN-gamma. By 6 to 12 h after LPS challenge, however, hepatic LPS-induced iNOS mRNA and serum nitrate/nitrite levels were reduced substantially in GKO mice. Residual LPS-induced iNOS mRNA in livers of GKO mice was nearly ablated by macrophage depletion, indicating that induction of iNOS mRNA in liver requires both endogenous IFN-gamma and either macrophages and/or macrophage-derived factors. TNFR1-mediated signaling was involved in the induction of LPS-induced iNOS mRNA in liver at 3 and 6 h, but not in its maintenance at 8 h. Conversely, induction of iNOS mRNA in spleen by LPS was independent of TNFR1-mediated signaling. Our results indicate that macrophages and/or their secreted products, endogenous IFN-gamma production, and TNFR1-mediated signaling play key roles in the in vivo regulation of iNOS mRNA expression and that the extent of their involvement is both time and organ specific.

Animals↗
PubMed1997

Changing trends in the incidence of non-Hodgkin's lymphoma in Europe. Biomed Study Group.

Non-Hodgkin's lymphoma (NHL) is not a uniform disease entity, and in order to investigate the reported changes in incidence we have set up a study in seven population-based cancer registries in Europe. The study is designed to look at changes in the incidence of total NHL and disease subgroups using standard definitions and methodology. The registries are based in Leeds, Dijon, Kuopio, Odense, Florence, Eindhoven, and Ragussa. The classification system we have used is based on the REAL classification and has utility for epidemiological studies. We have used it to convert data sets which have utilized both local cases and the ICD-O classification. In order to improve data reproducibility, CLL/LL, myeloma/MGUS, lymphoblastic disease, and Hodgkin's disease have been excluded because of the difficulty in defining incident cases accurately. The preliminary results of this study show that there is still an upward trend in incidence rate and that in Yorkshire this is 3% per annum in total NHL. The subgroups which are increasing are extranodal and nodal peripheral T-cell lymphoma. Similar increases in incidence have been reported for the other registries. We conclude that there is a continued upward trend in incidence of NHL, the causes of which are uncertain.

Europe↗
PubMed1996

A case of acute myelofibrosis with complex karyotypic changes: a type of myelodysplastic syndrome.

A 73-year-old woman developed a rapidly fatal disease that fit the clinical criteria for acute myelofibrosis. Over a 9 month period she progressed from normal peripheral blood counts to severe pancytopenia and finally a terminal phase with monocytosis and circulating myeloblasts. Morphologic examination of her bone marrow at presentation showed trilineage dysplasia, hypercellularity, and diffuse fibrosis with foci of immature precursors. Cytogenetic, analysis showed the karyotype 45-46, XX,del(5)(q33),+11,add(17)(q25),-18,-20,+22. The morphologic and cytogenetic findings in this case support a relationship between acute myelofibrosis and myelodysplastic syndromes. Acute myelofibrosis with complex chromosomal aberrations may represent one pathway of evolution in myelodysplasia that is associated with a particularly poor prognosis.

Acute Disease↗
PubMed1996

Stimulation of the ceramide pathway partially mimics lipopolysaccharide-induced responses in murine peritoneal macrophages.

Recent studies have suggested that lipolysaccharide (LPS) stimulates cells by mimicking the second-messenger function of ceramide, a lipid generated in the cell by the action of sphingomyelinase (SMase). To examine this possibility further, we compared the abilities of LPS, SMase, and/or ceramide analogs to induce cytokine secretion, modulate gene expression, and induce endotoxin tolerance in macrophages. SMase and LPS induced secretion of tumor necrosis factor alpha (TNF-alpha) to comparable degrees; however, unlike LPS, SMase failed to stimulate detectable interferon activity. Cell-permeable analogs of ceramide induced the expression of many LPS-inducible genes; however, the expression of interferon-inducible protein 10 (IP-10) and interferon consensus sequence-binding protein (ICSBP) mRNAs was significantly lower than that induced by LPS. Both SMase-induced TNF-alpha secretion and LPS-induced TNF-alpha secretion were inhibited by pretreatment with a serine/threonine phosphatase inhibitor, calyculin A. Macrophages preexposed in vitro to LPS to induce a well-characterized state of endotoxin tolerance secreted little or no TNF-alpha upon secondary challenge with either LPS or SMase, whereas macrophages preexposed to SMase secreted high levels of TNF-alpha upon secondary stimulation with LPS or SMase. Collectively, these results suggest that ceramide activates a subset of LPS-induced signaling pathways in murine peritoneal exudate macrophages.

Animals↗
PubMed1995

The serine/threonine phosphatase inhibitor, calyculin A, inhibits and dissociates macrophage responses to lipopolysaccharide.

LPS-stimulated macrophages (M phi) produce inflammatory mediators that are largely responsible for the pathophysiology associated with septic shock. M phi respond to LPS with rapid protein phosphorylation and dephosphorylation on serine, threonine, and tyrosine residues. If these events are critical for the cellular response to LPS, the kinases and/or phosphatases involved may be vulnerable targets for pharmacologic intervention. Recent studies demonstrated that tyrosine kinase inhibitors block LPS-induced tyrosine phosphorylation of MAP kinases as well as TNF-alpha and IL-1 beta production. To investigate a role for serine/threonine phosphatases, we evaluated the effect of calyculin A, a potent serine/threonine phosphatase inhibitor, on LPS stimulation of murine M phi. Pretreatment of M phi with calyculin A inhibited LPS-induced expression of six immediate-early genes: TNF-alpha, IL-1 beta, IFN-beta, IP-10, IRF-1, and TNFR-2. Calyculin A added 1.5 h after LPS treatment greatly reduced accumulation of IP-10, IRF-1, and TNFR-2 mRNA, but not TNF-alpha, IL-1 beta, and IFN-beta mRNA. Calyculin A, in the absence or presence of LPS, resulted in sustained tyrosine phosphorylation of the MAP kinases. These findings suggest that an "early" serine/threonine phosphatase activity is essential for LPS stimulation of M phi and that the activation of MAP kinases is not sufficient for the induction of these immediate-early genes. The requirement for a "late" phosphatase activity for expression of a subset of LPS-inducible genes dissociates at least two regulatory pathways in LPS signal transduction.

Animals↗
PubMed1994

The increasing incidence of non-Hodgkin's lymphoma (NHL): the possible role of sunlight.

This review critically examines the rise in incidence in non-Hodgkin's Lymphoma (NHL) in selected parts of the world and concludes that much of the increase is likely to be due to unknown biological factors. It postulates that one reasonable explanation for the rise in incidence of NHL is the ever increasing exposure of populations, particularly in the Northern Hemisphere, to sunlight. Support for the hypothesis is supplied from both epidemiological evidence and studies of the responses of lymphocytes to ultra-violet light in both in vitro and in vivo experimental work.

Humans↗
PubMed1989

Anxious mood and memory.

Influenced by Bower (Am. Psychol. 36, 129-148, 1981) and Lang (Anxiety and the Anxiety Disorders, Erlbaum, Hillsdale, N.J., 1985), we tested three hypotheses concerning anxious mood and memory: (1) the mood state dependent hypothesis which states that memory retrieval will be greater when mood at encoding and at recall are the same than when they are different: (2) the encoding mood congruent hypothesis which states that information semantically related to mood at encoding is retrieved more readily than information unrelated to mood at encoding; and (3) the recall mood congruent hypothesis which states that information semantically related to mood at recall is retrieved more readily than information unrelated to mood at recall. We induced anxiety in speech anxious students by informing them that they would be delivering a speech during the experiment. Mood could be either anxious or nonanxious at encoding, recall, both, or neither. Hence, there were four groups: Anxiety-Anxiety, Anxiety-Nonanxiety, Nonanxiety-Anxiety, and Nonanxiety-Nonanxiety. Subjects were asked to rate the self-descriptiveness of anxiety (e.g. NERVOUS) and nonanxiety adjective (e.g. POLITE) during the encoding phase, and to recall them later. Anxious mood was measured by self-report scales and by heart rate. No support was obtained for any of the three hypotheses. However, post-hoc analyses indicated that anxiety words were recalled least often in subjects whose heart rate increased from encoding to recall. This suggests that attention to threat information may diminish in aroused nonclinical subjects.

Adult↗
PubMed1989

Actuarial analysis of a uniform and reliable preservation method for viable heart valve allografts.

CryoLife has developed a method for cryopreserving allograft heart valves for transplantation. Since 1984, 6,907 valves have been processed and 4,216 transplanted. Documentation was available on 2,647 transplants, 11 of which were removed for structural deterioration and 13, for nonstructural deterioration. At the end of 35 months, actuarial survival was 99.17% and the estimated freedom from reoperation, 97.16%. There have been no reports of thromboembolism or valve-related death.

Actuarial Analysis↗