Interaction of family history of breast cancer and dietary antioxidants with breast cancer risk (New York,United States)

We sought to determine if specific dietary antioxidants may be particularly effective in reducing breast cancer risk for women reporting family history (FH) of breast cancer in a first-degree relative. Interviews regarding usual diet, health, and family histories were conducted with 262 premenopausal and 371 postmenopausal women with incident, primary breast cancer from western New York (United States). These women were frequencymatched by age and county of residence with community controls. Among premenopausal women, there was a significant interaction between FH and -tocopherol; -tocopherol was associated with significantly decreased risk among FH+ women (adjusted fourth-quartile odds ratio [OR]=0.01, 95 percent confidence interval [CI]=0.0–0.3). This association was much weaker for FH-women [OR=0.7, CI=0.4–1.2]. For FH-women, a significant inverse association was observed between -carotene and premenopausal breast-cancer risk (OR=0.4, CI=0.3–0.5), but not for FH+ women (OR=0.5, CI=0.1–4.0). Similar relationships, although not as strong, were noted among postmenopausal women. Although limited by small numbers, these results suggest that biologic mechanisms of tumorigenesis may differ in FH+ and FH-women, and that -tocopherol may be a potential chemopreventive agent for women with a family history of breast cancer, particularly premenopausal women.This research was conducted by the Department of Social and preventive Medicine, State University of New York at Buffalo. This publication is supported in part by grants CA11535 and 5 R25 CA1820117 from the US National Cancer Institute and PDT-434 from the American Cancer Society. Dr Freudenheim is a recipient of a Research Career Development Award from the National Cancer Institute (CA01633). This work is solely the responsibility of the authors and does not necessarily represent the views of the NCI.     

Effects of vitamin D3 metabolites on bone cell calcium transport

Summary The vitamin D₃ metabolite, 25-hydroxycholecalciferol, at concentrations of 0.01 to 10.0 g/ml, decreased calcium uptake by isolated bone cells. The effect occurred within 1 min after the simultaneous addition of metabolite and⁴⁵Ca. Lactic acid and ATP production by the cells was not affected. 24(R), 25-dihydroxycholecalciferol produced a similar decrease in calcium uptake. Vitamin D₃ had no effect at concentrations from 0.01 to 10.0 g/ml. No effect of 1,25-dihydroxycholecalciferol on calcium uptake was observed with concentrations from 0.1 to 100 ng/ml and various preincubation periods extending to 2 h. None of the agents had any effect on calcium efflux. The effects of 25-hydroxycholecalciferol and 24(R), 25-dihydroxycholecalciferol on calcium uptake were not seen in isolated fetal rat skin cell preparations.     

Quality assurance in a children's psychiatric hospital

The use of short-term isolation (STI) in a children's psychiatric hospital was examined using the Joint Commission on Accreditation of Hospitals (JCAH) quality assurance mode. A Clinical Care Evaluation addressed two questions: Are we providing quality use of STI? And are we adequately documenting its use? A medical record audit of 78 discharged patients and a review of unit records provided hospital staff with utilization and demographic statistics; structured interviews with staff and inpatients were conducted that provided information about their opinions of STI. The data gathered served as the basis for recommendations that led to planned, informed program changes.     

Are "pink puffers" more breathless than "blue bloaters"?

Breathlessness, disability, and exercise tolerance were assessed in 26 patients with severe chronic airflow limitation (forced expiratory volume in one second (FEV1) less than or equal to 1 litre) divided into two groups--15 patients who were normocapnic (pressure of arterial carbon dioxide (Paco2) less than 5.5 kPa (less than 41.4 mm Hg)), and 11 patients who were hypercapnic (Paco2 greater than 6 kPa (greater than than 45.1 mm Hg)). The two groups were well matched for spirometric values (FEV1 0.59 1 and 0.62 1, respectively). All of the hypercapnic patients could improve blood gas tensions towards normal by hyperventilation. There were no significant differences in visual analogue scores of breathlessness during treadmill exercise, disability (oxygen-cost diagram, dyspnoea grade), or exercise tolerance (six-minute walk, maximal consumption of oxygen during bicycle ergometry, distance walked to exhaustion in progressive treadmill test). The findings show that the "fight" to maintain normal blood gas tensions in the face of severe airflow limitation does not have an appreciable cost in terms of disability.     

Reduced cardiotoxicity of doxorubicin given in the form ofN-(2-hydroxypropyl) methacrylamide conjugates: an experimental study in the rat

Summary A rat model was used to evaluate the general acute toxicity and the late cardiotoxicity of 4 mg/kg doxorubicin (DOX) given either as free drug or in the form of threeN-(2-hydroxypropyl)methacrylamide (HPMA) copolymer conjugates. In these HPMA copolymers, DOX was covalently bound via peptide linkages that were either non-biodegradable (Gly-Gly) or degradable by lysosomal proteinases (Gly-Phe-Leu-Gly). In addition, one biodegradable conjugate containing galactosamine was used; this residue was targeted to the liver. Over the first 3 weeks after the i.v. administration of free and polymer-bound DOX, all animals showed a transient reduction in body weight. However, the maximal reduction in body weight seen in animals that received polymer-bound DOX (4 mg/kg) was significantly lower than that observed in those that received free DOX (4 mg/kg) or a mixture of the unmodified parent HPMA copolymer and free DOX (4 mg/kg;P<0.01). Throughout the study (20 weeks), deaths related to cardiotoxicity were observed only in animals that received either free DOX or the mixture of HPMA copolymer and free DOX; in these cases, histological investigations revealed marked changes in the heart that were consistent with DOX-induced cardiotoxicity. Sequential measurements of cardiac output in surviving animals that received either free DOX or the mixture of HPMA copolymer and free DOX showed a reduction of 30% in function beginning at the 4th week after drug administration. The heart rate in these animals was 12% lower than that measured in age-matched control rats (P<0.05). Animals that were given the HPMA copolymer conjugates containing DOX exhibited no significant change in cardiac output throughout the study (P<0.05). In addition, no significant histological change was observed in the hearts of animals that received DOX in the form of HPMA copolymer conjugates and were killed at the end of the study. However, these animals had shown a significant increase in heart rate beginning at 8 weeks after drug administration (P<0.01). This study demonstrates that covalent binding of DOX to HPMA copolymer conjugates via both stable and biodegradable peptidyl linkages considerably reduces both the general acute toxicity and the late cardiotoxicity of DOX in the rat and could offer the potential for improving the therapeutic index in the clinical application of DOX.     

Primary cerebral lymphoma: a study of 47 cases probed for Epstein-Barr virus genome.

AIMS: To determine the prevalence of Epstein-Barr virus genome in primary cerebral lymphomas occurring in the absence of immune suppression. METHODS: Forty eight consecutive patients with lymphomas restricted to the central nervous system were identified, all of whom had had neurosurgical biopsies performed at the National Hospitals for Neurology and Neurosurgery, London. Only five patients had some form of underlying immune deficiency; 43 were apparently normal. The tumours were studied with immunohistochemical markers and by in situ hybridisation, using a biotinylated probe to the internal repeat region of Epstein-Barr virus. RESULTS: All the lymphomas were B cell in origin. Tumours from the five immunosuppressed patients all showed hybridisation, as did two of the "spontaneous" tumours. CONCLUSIONS: This is the largest series of cerebral lymphomas so far probed for Epstein-Barr virus genome: as more are examined, it is suggested that a small proportion of the tumours from immunocompetent patients will also contain the virus.     

Use of an electrocardiograph to record the skin-resistance response with a new type of electrode

A new method is described for recording the emotion-induced decrease in skin resistance area, which is known as the skin-resistance response (SRR). The method employs a simple current source and a new type of tetrapolar electrode in which the SRR is measured with the non-current-carrying electrodes. The signal produced can be recorded with a standard electrocardiograph. Typical SRRs from two subjects are presented.     

Effects of 2,4-dinitrophenol amylobarbitone and certain other drugs on the rate of oxygen consumption and force of contraction of isolated curarized diaphragm muscle of the rat

1 A technique has been developed for studying over periods of 10 min or longer the effects of drugs on both the force of electrically-induced contractions and the oxygen consumption of an isolated, curarized, mammalian, skeletal muscle preparation.2 The resting oxygen consumption of the muscle was increased substantially by 2,4-dinitrophenol in concentrations (0.02 mM and higher) that eventually produced contracture. Two other uncoupling agents, 4,6-dinitro-o-cresol and carbonylcyanide-p-trifluoromethoxyphenylhydrazone, behaved similarly.3 The oxygen consumption over 10 min of the stimulated muscle was also increased by 2,4-dinitrophenol (0.05 mM), although the strength of the `maximal'' contractions was lessened.4 Amylobarbitone increased the strength of contraction at a concentration (0.2 mM) that did not affect oxygen consumption significantly. Amylobarbitone and pentobarbitone also increased it at a concentration (1 mM) that depressed oxygen consumption. They decreased both strength of contraction and oxygen consumption at a concentration of 5 mM. Phenobarbitone had a weaker action.5 S-n-decyl-thiouronium increased oxygen consumption when given at a concentration (1 mM) that diminished strength of contraction and eventually produced contracture of the muscle.6 Both S-methyl-thiouronium (1 mM) and 4-aminopyridine (0.1 mM and 0.5 mM) increased strength of contraction without increasing oxygen consumption. Neither strength of contraction nor oxygen uptake was affected by ouabain (up to 0.01 mM) or by phenformin (0.1 mM).7 It is concluded that the response to 2,4-dinitrophenol is due mainly, if not wholly, to its known ability to uncouple oxidative phosphorylation; that the response to the barbiturates is due to a combination of a known metabolic action (viz., blocking of the respiratory chain) and a stimulant action on muscle; and the response to S-n-decyl-thiouronium to a disruptive action on cell membranes. The disproportionate actions of 4-aminopyridine and S-methyl-thiouronium on strength of contraction relative to oxygen consumption are also attributed to a non-metabolic action.     

Evaluation of patients undergoing lung volume reduction surgery: ancillary information available from computed tomography

AIM: A number of imaging techniques have been used for the pre-operative assessment of patients for lung volume reduction surgery (LVRS). We evaluated whether data currently acquired from perfusion scintigrams and cine MR of the diaphragm are obtainable from high resolution CT (HRCT) of the thorax. MATERIALS AND METHODS: Thirty patients taking part in a randomized controlled trial of LVRS against maximal medical therapy were evaluated. HRCT examinations (n= 30) were scored for (i) the extent and distribution of emphysema; (ii) the extent of normal pulmonary vasculature; and (iii) diaphragmatic contour, apparent defects and herniation. On scintigraphy, (n= 28), perfusion of the lower thirds of both lungs, as a proportion of total lung perfusion (LZ/T(PERF)), was expressed as a percentage of predicted values (derived from 10 normal control subjects). On cine MR (n= 25) hemidiaphragmatic excursion and coordination were recorded. RESULTS: Extensive emphysema was present on HRCT (60% +/- 13.2%). There was strong correlation between the extent of normal pulmonary vasculature on HRCT and on perfusion scanning (r(s)= 0.85, P< 0.00005). Hemidiaphragmatic incoordination on MR was weakly associated with hemidiaphragmatic eventration on HRCT (P= 0.04). CONCLUSION: The strong correlation between lung perfusion assessed by HRCT and lung perfusion on scintigraphy suggests that perfusion scintigraphy is superfluous in the pre-operative evaluation of patients with emphysema for LVRS.     

Randomised controlled trial of advice on an egg exclusion diet in young children with atopic eczema and sensitivity to eggs

Background: The role of exclusion diets in the management of atopic eczema in young children is uncertain. This randomised controlled trial evaluates the effect of excluding egg from the diet in young children with atopic eczema and sensitivity to eggs. Fifty-five such children were randomised either to a 4-week regimen, in which mothers were given general advice on care of eczema and additional specific advice from a dietician about an egg exclusion diet (diet group), or to a control group in which general advice only was given. Both groups continued conventional topical treatment. Disease activity was assessed by estimates of the surface area affected by eczema and by an arbitrary severity score. Possible egg sensitivity was identified by RAST before randomisation and after the trial by double-blind placebo-controlled egg challenge. Results: The mean reduction in surface area affected by eczema was significantly greater (p = 0.02) in the group receiving dietary advice (from 19.6% to 10.9% area affected) than in the control group (from 21.9% to 18.9%). A significant improvement also occurred in severity score (p=0.04): from 33.9 to 24.0 units for the diet group compared with a decrease from 36.7 to 33.5 in the control group. The study suggests that advice on the dietary exclusion of eggs is useful as part of the overall management of young children with atopic eczema and sensitivity to eggs.