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C Rose

Publications and source records attributed to C Rose.

At least 19 recordsLinked to original sources
PubMed1998

[Clinics for counseling on cancer genetics. Experiences with genetic studies and counseling on familial breast cancer and colorectal cancer].

Five to ten percent of cases of breast cancer and colorectal cancer are familial. These families can be divided into high-risk families and moderate-risk families. Cancer in high-risk families can often be explained by dominant inheritance of a gene causing increased susceptibility to cancer. There is a great demand for genetic counseling in these families, and the structure of and experiences from a familial cancer clinic at Odense University Hospital is described. The establishment of a familial cancer clinic involves three steps: 1) Identification of families with increased cancer susceptibility; 2) Molecular tests to identify gene carriers; 3) Clinical examinations for early detection of tumors. Achievement of these three steps requires the involvement of several medical specialties to ensure patient care. Experience with familial cancer clinics is still limited and the involvement of genetic testing and clinical examination programs at risk individuals are insufficiently examined. The rapidly improving techniques for genetic testing make it urgent that it is implemented as part of already established clinical programs.

Adult↗
PubMed1998

Evidence for altered central noradrenergic function in experimental acute liver failure in the rat.

These is increasing evidence to suggest that central noradrenergic mechanisms may contribute to the central nervous system manifestations of acute liver failure. To further elucidate this possibility, extracellular brain concentrations of the monoamines, noradrenaline (NA), dopamine (DA), and serotonin, were measured by high-performance liquid chromatography with electrochemical detection in microdialysates from the extracellular compartment of frontal cortex in rats with acute (ischemic) liver failure at various times during the progression of encephalopathy and brain edema, as well as in obligate control groups of animals. In addition, binding sites for the noradrenergic receptor subtype ligands, [3H]-prazosin (alpha1 sites), [3H]-RX821002 (alpha2 sites), and [125]I-iodopindolol (beta sites), were assessed using quantitative receptor autoradiography in regions of the brains of rats at coma stage of acute liver failure and of control groups of animals. Coma stages of encephalopathy in acute liver failure were associated with selectively increased noradrenaline concentrations (P < .05) and a concomitant selective loss of alpha1 and beta1 sites in frontal cortex and thalamus. These findings add to a growing body of evidence that central noradrenergic function is modified in acute liver failure and suggest that alpha1/beta1 receptor-mediated noradrenergic mechanisms may play a role in the pathogenesis of brain edema and encephalopathy in this condition.

Adrenergic alpha-Antagonists↗
PubMed1998

Acquisition of nicotine self-administration in rats: the effects of dose, feeding schedule, and drug contingency.

The studies presented here were designed to further clarify the nature of nicotine self-administration (SA) based on a limited access model in which rats are food restricted, receive operant training using food reinforcement, and are then tested in daily 1-h drug sessions. We examined the effects of dose, feeding schedule, and contingency of drug delivery on acquisition of nicotine SA. Two doses of nicotine bitartrate, 0.03 and 0.06 mg/kg per infusion (free base), supported the transition from food-reinforced to drug-reinforced responding, although the pattern of behavior differed between these doses. In contrast, 0.01 mg/kg per infusion failed to maintain nicotine SA. In a second study, animals were divided into three groups according to feeding schedule. Rats that were both weight restricted and food deprived showed the highest level of SA behavior, although neither food deprivation nor weight restriction was necessary to establish SA. In the third experiment, rats that were switched from food to nicotine as the response-dependent reinforcer maintained higher response rates throughout a 9-day period than animals switched to response-independent (i.e., yoked) nicotine which showed minimal responding after day 1. Furthermore, the differences between self-administering and yoked animals emerged during the first session, suggesting that nicotine may serve as a reinforcer during the first drug exposure in naive animals. These results indicate that acquisition of nicotine SA can be influenced by both dose of nicotine and feeding schedule and that, in animals previously trained on a food-reinforced operant, active lever pressing is maintained only when nicotine delivery is contingent upon responding.

Animals↗
PubMed1998

Expression of CD30 on T helper cells in the inflammatory infiltrate of acute atopic dermatitis but not of allergic contact dermatitis.

The CD30 molecule has been proposed as a marker for a subset of CD4+CD45RO+ (memory) T cells with potent B cell helper activity producing IL-5 and IFN-gamma and as a specific marker for Th2 cells. Recently, an association has been demonstrated between elevated serum levels of soluble CD30, which is shed by CD30+ cells in vitro and in vivo, and atopic dermatitis but not respiratory atopic disorders or allergic contact dermatitis. We studied the expression of CD30 in the inflammatory infiltrate of atopic dermatitis compared with that of allergic contact dermatitis, with special regard to skin disease activity (acute vs subacute/ chronic). Biopsies were obtained from 16 patients suffering from atopic dermatitis (acute n = 6, subacute/ chronic n = 10), from 7 patients with acute allergic contact dermatitis and from 5 positive patch-test reactions. Paraffin-embedded as well as snap-frozen material was stained with anti-CD30 and anti-CD45RO mAbs according to standard procedures. Double-staining procedures for CD30CD3, CD30CD4, CD30CD45RO and CD30CD68 were also performed. Abundant CD45RO+ cells were detected both in atopic dermatitis and in allergic contact dermatitis lesions. We found scattered CD30+ cells in only one of six formalin-fixed paraffin-embedded acute atopic dermatitis biopsies, but in all of the respective snap-frozen specimens, possibly because CD30 expression on atopic dermatitis infiltrating cells is weak and sensitive to formalin fixation and paraffin embedding. CD30CD3 and CD30CD4 double staining identified CD30+ cells to be helper T lymphocytes. No significant CD30 expression (either in paraffin-embedded or in frozen material) could be found in subacute/chronic atopic dermatitis lesions or in any of the specimens of allergic contact dermatitis. The results suggest a specific regulatory function of CD30+ T cells in acute atopic dermatitis. With respect to the view that CD30 is a marker for Th2 cells, our observations confirm previous findings that Th2 cells predominate in the infiltrate particularly of acute atopic dermatitis. CD30 expression in acute atopic dermatitis but not in acute allergic contact dermatitis might be helpful in the histological differentiation of these disorders and in the further characterization of atopy patch testing.

Acute Disease↗
PubMed1998

The role of corticosteroids in nicotine's physiological and behavioral effects.

This paper reviews evidence indicating that adrenal corticosteroids modulate the responsiveness of mice and rats to nicotine. Adrenalectomy increases, and both acute and chronic corticosteroid administration decrease, some of the physiological and behavioral effects of nicotine. One function of adrenal steroids may be to regulate stress-induced changes in nicotine sensitivity. Another is to mediate the development of chronic tolerance when nicotine is given intermittently, and when the resulting tolerance has a learned component. A role of glucocorticoids in the development of tolerance to nicotine is suggested by the findings that a conditioned elevation of plasma corticosterone, which anticipates nicotine delivery, accompanies the development of chronic tolerance and that environmental cues evoke a conditioned corticosterone response, but only after they have become associated with nicotine delivery. The mechanisms by which adrenal steroids modulate nicotine sensitivity are not known, although recent in vitro evidence suggests that steroids can rapidly and reversibly reduce nicotinic receptor function. While most of the data are consistent with the hypothesis that corticosteroids reduce nicotine responsiveness, and thus promote a learned form of tolerance, there are new findings that corticosteroids increase the development of sensitization to the locomotor-activating effects of nicotine. These data suggest that formulations postulating a unidirectional effect of corticosteroids on nicotine's actions (e.g. decreased sensitivity) must be revised to take into account interacting variables such as the specific nicotine effect being studied and whether that effect normally exhibits tolerance or sensitization. Finally, research is presented which indicates that the corticosterone-elevating effects of nicotine, previously reported for experimenter-administered drug, are also produced when nicotine administration is contingent on an operant response, and at a dose which sustains the development of nicotine self-administration in rats. These findings highlight the feasibility of using self-administration models in future explorations of the relationship between adrenal steroids and nicotine function.

Adrenal Cortex Hormones↗
PubMed1998

The importance of surgery and accurate axillary staging for survival in breast cancer.

AIMS: The purpose of this study was to investigate, within the context of the Danish Breast Cancer Cooperative Group (DBCG) programmes, whether a dedicated surgical approach had a significant bearing on the outcome of breast cancer treatment. METHODS: From 1 January 1980 to 31 December 1990, patients below 70 years of age with operable breast cancer from Odense University Hospital (n=743) were compared with those from the rest of Denmark (denoted rest-DK) (n=15,419). All patients were treated according to nationwide DBCG guidelines and reported to the DBCG Data Centre. The potential median observation time was 11.2 years (range 6.0-16.9). Patients underwent mastectomy or breast conserving therapy, and high risk lymph-node positive patients had adjuvant systemic therapy with or without radiotherapy. RESULTS: Comparing total patients series, overall survival (OS) was significantly superior in patients from Odense compared with rest-DK (P=0.02), with 10-year OSs of 62% (95% CI: 58-65%) and 56% (55-57%), respectively. In subgroups, the OS of low-risk node negative patients (protocol A) in Odense compared with rest-DK was significantly better (P=0.02); 10-year OS was 78% (73-84%) versus 72% (70-73%). Among the high-risk pre-menopausal patients (protocol B), the OS was significantly better in Odense (P=0.009); 10-year OS was 67% (60-75%) versus 53% (51-55%) in rest-DK. Post-menopausal high-risk patients (protocol C) did not differ significantly in OS between Odense and rest-DK (P=0.61). Locoregional control in the Odense series was superior compared with rest-DK. More lymph nodes were recovered and examined from the axilla in the Odense series than in rest-DK, a median of 10 vs. 6 nodes. In the Odense series, a significantly higher proportion of pre-menopausal patients had positive lymph nodes, predominantly one to three positive nodes, and subsequently a lower proportion of pre-menopausal patients had negative lymph nodes compared with rest-DK (P=0.02), indicating a more accurate staging in Odense vs. rest-DK. The survival benefit among the patients from Odense cannot be explained by stage migration alone, but seems to represent a true survival advantage. Overall mortality was significantly lower in the Odense series compared with rest-DK. Whether or not this difference could be explained by lower background mortality in the Odense series or was caused by superior treatment is discussed. CONCLUSIONS: The extent of surgery seems important for locoregional tumour control and accurate axillary lymph-node staging. In combination, these might lead to superior recurrence-free and overall survival, although differences in background mortality cannot be ignored. Surgery, therefore, might represent a risk factor by itself.

Adult↗
PubMed1998

A woman's build and the risk of breast cancer.

A woman's build and the risk of breast cancer seem to be related. While relative overweight, as described by the body mass index, seems to be associated with increased breast cancer risk in postmenopausal women, overweight in premenopausal women seems slightly protective. Papers from a MEDLINE search are reviewed regarding the association between build and the development of breast cancer. Different aspects of build, such as height, weight, body mass index and body shape, are discussed. The more prominent associations found through this search are a positive association between height and breast cancer risk both in pre- and postmenopausal women. Regarding body mass index, the association is negative in premenopausal women and positive in postmenopausal women. Body shape described as masculine versus feminine seems to have no impact on breast cancer risk in premenopausal women, but seems to be positively associated with breast cancer in postmenopausal women. Possible biological mechanisms responsible for the associations with breast cancer risk are discussed, including endogenous oestrogens, androgens and glucose metabolic substances. Avoiding or reducing postmenopausal overweight may modify breast cancer risk indicators in a more favourable direction.

Body Mass Index↗
PubMed1998

L-ornithine-L-aspartate in experimental portal-systemic encephalopathy: therapeutic efficacy and mechanism of action.

Strategies aimed at the lowering of blood ammonia remain the treatment of choice in portal-systemic encephalopathy (PSE). L-ornithine-L-aspartate (OA) has recently been shown to be effective in the prevention of ammonia-precipitated coma in humans with PSE. These findings prompted the study of mechanisms of the protective effect of OA in portacaval-shunted rats in which reversible coma was precipitated by ammonium acetate administration (3.85 mmol/kg i.p.). OA infusions (300 mg/kg/h, i.v) offered complete protection in 12/12 animals compared to 0/12 saline-infused controls. This protective effect was accompanied by significant reductions of blood ammonia, concomitant increases of urea production and significant increases in blood and cerebrospinal fluid (CSF) glutamate and glutamine. Increased CSF concentrations of leucine and alanine also accompanied the protective effect of OA. These findings demonstrate the therapeutic efficacy of OA in the prevention of ammonia-precipitated coma in portacaval-shunted rats and suggest that this protective effect is both peripherally-mediated (increased urea and glutamine synthesis) and centrally-mediated (increased glutamine synthesis).

Ammonia↗
PubMed1998

Prognostic significance of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in primary breast cancer.

The uPA-mediated pathway of plasminogen activation is central to cancer metastasis. Whether uPA and PAI-1 are related to local recurrence, metastatic spread or both is not clear. We present a retrospective study of 429 primary breast cancer patients with a median follow-up of 5.1 years, in which the levels of uPA and PAI-1 in tumour extracts were analysed by means of an enzyme-linked immunosorbent assay. The median values of uPA and PAI-1, which were used as cut-off points, were 4.5 and 11.1 ng mg(-1) protein respectively. The levels of uPA and PAI-1 were correlated with tumour size, degree of anaplasia, steroid receptor status and number of positive nodes. Patients with high content of either uPA or PAI-1 had increased risk of relapse and death. We demonstrated an independent ability of PAI-1 to predict distant metastasis (relative risk 1.7, confidence limits 1.22 and 2.46) and that neither uPA nor PAI-1 provided any information regarding local recurrence.

Adult↗
PubMed1998

Enzyme-linked immunosorbent assay of epidermal growth factor receptor in lung cancer: comparisons with immunohistochemistry, clinicopathological features and prognosis.

The prognostic role of epidermal growth factor receptor (EGFR) remains controversial in patients with lung cancer. Previous assays for EGFR have primarily been qualitative or, at best, semiquantitative. In the present study, using fresh-frozen tissue from 190 unselected lung cancer patients, quantification of EGFR (EGFR(ELISA)) using a recently developed enzyme-linked immunosorbent assay (ELISA) technique was compared with results (EGFR(IHC)) obtained using immunohistochemistry (IHC). Correlation between results obtained by the two different techniques was highly significant (r(s) = 0.63, P < 0.001, n = 190). This correlation improved even further (r(s) = 0.76) when sections were estimated using an IHC score that took into account percentage staining, intensity and relative tumour area. Furthermore, the relationship between clinicopathological features and prognosis was identical for the two methods. The expression of EGFR was highest in squamous cell carcinomas, but it was not correlated with other characteristics such as age, sex, histological grading, stage or prognosis. We conclude that evaluation of EGFR content using IHC and ELISA produces comparable results.

Adult↗
PubMed1998

Nurses' attitudes to the use of alternative medicine in cancer patients.

This study reports results from a questionnaire study on nurses' attitudes to and experiences with alternative medicine, especially related to cancer patients' use of alternative medicine. Sixty nurses from a department of oncology and haematology participated in the study. The response rate was 62%. The nurses primarily perceived the use of alternative medicine as an individual choice which the nurses wanted to support. Sixty-three percent of the nurses indicated that alternative medicine could be useful in the treatment of cancer patients, 32% would sometimes suggest alternative medicine to the patients, and 20% used alternative medicine in their nursing. One-third of the nurses had experienced conflict in connection with alternative medicine and their patients, mostly when established treatment was delayed or refused in favour of alternative medicine. Fifty-three percent of the nurses had tried alternative medicine themselves. This study reveals that nurses are in an ambiguous and complex situation: they are simultaneously professionals in the established health care system, caregivers supporting the patients, and individuals using alternative medicine.

Adult↗
PubMed1998

Angiogenesis in breast cancer: a comparative study of the observer variability of methods for determining microvessel density.

The purpose of this study was to evaluate the reliability of different methods for estimating neovascularization in breast cancer and to compare them in terms of observer variability. The microvessel endothelium was stained immunohistochemically by antibodies against CD34. The investigated methods included Chalkley counting, estimation of intratumoral microvessel density (MVD) by one hot-spot, MVD by the mean value of three hot-spots, and the highest value of MVD in three hot-spots. In addition, we applied stereology in the quantification of angiogenesis in the whole tumor section by random and systematically distributed sampling fields. Each of forty tumors was measured with all methods, twice by the same observer and once by another observer. Observer variation was analyzed by orthogonal regression, estimating the slope and intercepts with 95% confidence intervals (CI), and by analysis of agreement using difference plots. Intraobservationally, the methods had variations of the same magnitude (coefficient of variation [CV] approximately 20%). Interobservationally, the stereologic estimate of vessel profiles, Q(A), from the whole tumor section and the Chalkley counting method had the lowest variation (CV approximately 21%), with a small contribution by observers alone (CV 8% to 9%). Interobservationally, the MVD methods had considerable variation with a large contribution by observers alone (CV approximately 30%), which was lowest using the mean of three hot-spots. Correlation slope and 95% CI of Chalkley were 1.18 (0.95, 1.48), CV 20%; slope of MVD (mean) was 1.14 (0.91, 1.43), CV 31%; and slope of MVD (max) was 1.15 (0.92, 1.45), CV 36%. The slope of MVD on one hot-spot was 1.33 (1.08, 1.63); CV 38%. Additional measurements performed using a conference microscope, eliminating subjectivity in hot-spot selection and field sampling, optimized the reproducibility: slope was 1.02 (0.99, 1.04); CV of differences, 3.5%. On the other hand, reproducibility was not necessarily optimized by choosing the same hot-spot area, because variation in selecting a microscopic field could yield different counting numbers. The stereologic estimation of QA based on the whole tumor section had a high reproducibility, with low variation due to observers. The Chalkley and MVD methods had moderate reproducibility, and the Chalkley method had low variation due to observers alone. For all methods, the biologic variation among patients was the major contributor to the total variation. The Chalkley and MVD methods have been published to provide significant prognostic estimates in breast cancer, but the Chalkley method has less observer variation and may be superior from a methodologic point of view.

Antigens, CD↗
PubMed1997

Use of record linkage between a statewide genetics service and a Birth Defects/Congenital Malformations Register to determine use of genetic counselling services.

The Birth Defects/Congenital Malformations Register of the Victorian Department of Human Services contains detailed, confidential information on over 2,000 babies born with a birth defect each year in Victoria, Australia, representing approximately 3% of the annual number of births. For 1991 and 1993, the type of anomaly was categorised as warranting a high, moderate, or low need of referral for genetic counselling, depending on risk of recurrence and possible genetic cause. The Victorian Clinical Genetics Service at the Murdoch Institute, Melbourne, offers free, centralised genetic counselling services for the entire state. A comparison of case records between the two agencies has shown little difference in overall use of genetic counselling between 1991 (17%) and 1993 (16%). Rate of uptake in the "high need" category improved only slightly during that period, from 40% in 1991 to 43% in 1993. Utilization of genetic counselling services did not vary disproportionately with mother's country of birth, but was higher for older mothers. As was expected, rates were highest when a baby was born at the only hospital that provides on-site genetic counselling services. Even where a statewide genetic counselling service is in place, it is disappointing that over half of those judged at high need for genetic counselling are not making use of this service. This study will provide baseline information to which future studies can be compared. Using the same study methodology, it will be possible to examine whether the uptake rate increases in accordance with increased genetic services.

Congenital Abnormalities↗
PubMed1997

Postoperative radiotherapy in high-risk premenopausal women with breast cancer who receive adjuvant chemotherapy. Danish Breast Cancer Cooperative Group 82b Trial.

BACKGROUND: Irradiation after mastectomy can reduce locoregional recurrences in women with breast cancer, but whether it prolongs survival remains controversial. We conducted a randomized trial of radiotherapy after mastectomy in high-risk premenopausal women, all of whom also received adjuvant systemic chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF). METHODS: A total of 1708 women who had undergone mastectomy for pathological stage II or III breast cancer were randomly assigned to receive eight cycles of CMF plus irradiation of the chest wall and regional lymph nodes (852 women) or nine cycles of CMF alone (856 women). The median length of follow-up was 114 months. The end points were locoregional recurrence, distant metastases, disease-free survival, and overall survival. RESULTS: The frequency of locoregional recurrence alone or with distant metastases was 9 percent among the women who received radiotherapy plus CMF and 32 percent among those who received CMF alone (P<0.001). The probability of survival free of disease after 10 years was 48 percent among the women assigned to radiotherapy plus CMF and 34 percent among those treated only with CMF (P<0.001). Overall survival at 10 years was 54 percent among those given radiotherapy and CMF and 45 percent among those who received CMF alone (P<0.001). Multivariate analysis demonstrated that irradiation after mastectomy significantly improved disease-free survival and overall survival, irrespective of tumor size, the number of positive nodes, or the histopathological grade. CONCLUSIONS: The addition of postoperative irradiation to mastectomy and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal women with breast cancer.

Adult↗