Care of Seniors with Breast Cancer - Treatment Received and Refining Decision Making.

AIMS: Treatment decisions for older patients with breast cancer are complex and evidence is largely extrapolated from younger populations. Frailty and comorbidity need to be considered. We studied the baseline characteristics and treatment decisions in older patients in Christchurch with breast cancer and assessed survival outcomes and prognostic/discriminatory performance of several tools. MATERIALS AND METHODS: We searched the Canterbury Breast Cancer Registry and identified patients aged 70 years or older at diagnosis with invasive, non-metastatic breast cancer between 1 June 2009 and 30 June 2015. We retrieved demographics, treatment and outcome information. Overall survival and breast cancer-specific survival were estimated. Tools analysing performance status and comorbidity were assessed for their prognostic and discriminatory power. RESULTS: In total, 440 patients were identified. Primary surgery was carried out for 362 patients (82.3%): breast-conserving surgery in 114 (of whom 88.6% received radiation therapy); mastectomy in 248 (of whom 24.6% received radiation). Hormone therapy was given for 265 (71.1%) patients with oestrogen receptor-positive cancers. Two hundred and seventy-four (62.3%) patients received full standard treatment, which was associated with significantly improved 5-year survival and 5-year breast cancer-specific survival. The median estimated overall survival was 8.2 years (95% confidence interval 7.3-9.1 years). Of those who died, 71.3% of deaths were due to causes other than breast cancer or unknown causes. The comorbidity-adjusted life expectancy (CALE) showed partial prognostic accuracy. CALE, Charlson and Eastern Cooperative Oncology Group tools all showed discriminatory value. CONCLUSION: In this population-based series of older patients with breast cancer, showing high levels of primary and adjuvant treatment, patients were more likely to die of causes other than breast cancer. Performance status and comorbidity tools showed prognostic and discriminatory potential in this population supporting their use in treatment decision making. CALE showed the most potential to improve treatment decisions but requires validation in this population to improve prognostic accuracy.

Effect of alum treatment on the trihalomethane formation and bacterial regrowth potential of natural and synthetic waters.

Waters from five reservoirs and "synthetic waters", prepared using terrestrially derived dissolved organic matter (DOM) extracted from vegetation and reservoir catchment soils, were studied for their treatability with alum using a jar test procedure. DOM in drinking water is a precursor for the formation of trihalomethanes (THM) following chlorine disinfection and can also be a substrate for microbial growth in the drinking water distribution system. The trihalomethane formation potential (THMFP) represents an upper concentration limit on THMs formed by chlorination, while bacterial regrowth potential (BRP) is an indicator of the bioavailability of DOM. BRP and THMFP were measured before and after alum treatment and the results were related to the source of the DOM. It was found that freshly derived terrestrial DOM in synthetic water resulted in higher THMFP and BRP than DOM in reservoir waters. For the samples investigated, conventional alum treatment did not always reduce the THM precursor levels formed in laboratory tests below the NH&MRC (1996) guideline level of 250 microg/L nor produce microbially stable waters.

Smoking habits in a cohort of U.K. adolescents.

Active smoking is an increasing problem amongst U.K. teenagers. The smoking habits of a cohort of 14-16-year-olds were determined and the association between regular active smoking and domestic and social factors investigated. Current smoking habits of a cohort of 2289 14-16-year-olds were assessed using a simple postal questionnaire. Data concerning potential factors associated with active smoking were collected from questionnaire completed by parents. Nine hundred and sixty-nine (44.8%) children admitted to having smoked at some time, with 562 (30.0%) having smoked in the previous 12 months. Three hundred and six (14.1%) children were regular smokers and 158 (51.6% of regular smokers, 7.3% of total cohort) smoked daily. Age, number of other children in the household, parental smoking, smoking sibling(s) and living in a single parent household were all independently associated with regular smoking. Regular smoking was a significant problem amongst this cohort of teenagers. Living with other smokers, age, household size and living with one parent all predicted a regular smoking habit.

Anxiety and depression in severe chronic obstructive pulmonary disease: the effects of pulmonary rehabilitation.

BACKGROUND: Previous studies have demonstrated high levels of anxiety and depression among patients with chronic obstructive pulmonary disease (COPD). The effects of an outpatient pulmonary rehabilitation (PR) program on psychological morbidity were examined in patients with severe COPD. METHODS: Levels of anxiety and depression in 95 patients with severe COPD (FEV1 < 40% predicted) were measured on entry to an outpatient PR program using the Hospital Anxiety and Depression (HAD) scale. HAD scores were remeasured at the completion of PR (3 months) and at 6 month follow-up. The effects of PR on mean HAD scores and on the number of patients with significant anxiety or depression were determined. Improvements in exercise capacity after PR were compared in patients with high and low HAD scores. RESULTS: Of patients, 35 (29.2%) had significant anxiety at screening and 18 (15%) significant depression. PR produced statistically significant falls in mean HAD scores for anxiety and depression, both of which remained significantly lowered at 6-month follow-up. PR also reduced the number of patients with significant anxiety or depression. Patients with high anxiety levels showed significantly greater improvements in shuttle walk distance than those with low HAD scores. CONCLUSIONS: Levels of anxiety and depression were high in a significant minority of this group of patients with severe COPD and were significantly improved by PR. Patients with higher HAD scores had lower baseline shuttle walk distances than those with low HAD scores. Anxious patients showed statistically greater improvements in exercise capacity following PR.

The natural history of respiratory symptoms in a cohort of adolescents.

A cohort of 2,289 children, previously studied at the age of 6-8 yr, were followed up by means of a postal questionnaire when aged 14 -16 yr to examine the association between potential risk factors and the natural history of respiratory symptoms. Children with current symptoms, persistent symptoms, and late-onset symptoms were identified and multivariate analyses were performed to determine the independent association between risk factors and these various symptom-based subgroups. Personal and family history of atopy was significantly associated with all symptom groups and with the presence of doctor-diagnosed asthma. Smoking, either active or passive, was shown to be significantly associated with current, persistent, and late-onset symptoms. Other factors shown to be significantly associated with certain symptom groups were gender (late-onset wheeze), single-parent households (current cough, persistent cough), social class (late-onset wheeze), number of children in the household (persistent wheeze, late-onset cough), number of furry pets in the household (current wheeze), birth weight (late-onset wheeze), and gas cookers (current wheeze, persistent wheeze). In a subgroup of children studied in more detail in 1987, bronchial hyperresponsiveness in 1987 was positively associated with persistent wheeze in 1995, whereas positive skin-prick testing in 1987 was not.

Effects of 0.2 ppm ozone on biomarkers of inflammation in bronchoalveolar lavage fluid and bronchial mucosa of healthy subjects.

Short-term exposure to ozone at peak ambient levels induces neutrophil influx and impairs lung function in healthy humans. In order to investigate the mechanisms contributing to neutrophil recruitment and to examine the role of T-cells in the acute inflammatory response, we exposed 12 healthy humans to 0.2 parts per million (ppm) of ozone and filtered air on two separate occasions for 2 h with intermittent periods of rest and exercise (minute ventilation = 30 L x min(-1)). Fibreoptic bronchoscopy was performed 6 h after the end of exposures. Total protein, tryptase, histamine, myeloperoxidase, interleukin (IL)-8 and growth-related oncogene-alpha (Gro-alpha) were measured and total and differential cell counts were performed in bronchoalveolar lavage (BAL) fluid. Flow cytometry was performed on BAL cells to study total T-cells, T-cell receptors (alphabeta and gammadelta), T-cell subsets (CD4+ and CD8+ cells) and activated T-cell subsets (CD25+). Using immunohistochemistry, neutrophils, mast cells, total T-cell numbers, T-cell subsets, CD25+ T-cells and leukocyte endothelial adhesion molecules including P-selectin, E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 were quantified in the bronchial biopsies. Paired samples were available from nine subjects. Following ozone exposure there was a threefold increase in the proportion of polymorphonuclear neutrophils (PMNs) (p=0.07) and epithelial cells (p=0.05) in BAL fluid. This was accompanied by increased concentrations of IL-8 (p=0.01), Gro-alpha (p=0.05) and total protein (p=0.058). A significant positive correlation was demonstrated between the two chemokines and proportion of PMNs in BAL fluid. After ozone exposure there was a significant decrease in the CD4/CD8 ratio (p=0.05) and the proportion of activated CD4+ (p=0.01) and CD8+ T-cells (p=0.04). However, no significant changes were demonstrable in any of the inflammatory markers studied in the biopsies. Short-term exposure of healthy humans to 0.2 ppm ozone induced a neutrophil influx in peripheral airways at 6 h post exposure, but no apparent inflammatory response in proximal airways. This response seems to be mediated at least in part by interleukin-8 and growth-related oncogene-alpha.

Substance-Induced Psychosis.

Intoxication and withdrawal from a variety of central nervous system depressants and stimulants may induce hallucinations or delusions, which, when unaccompanied by insight, are the hallmarks of psychosis. A substance-induced psychosis may, in many instances, present as an organic psychosis or as an independent mental disorder (eg, schizophrenia), complicating diagnostic efforts. Ramifications of a misdiagnosed psychotic illness are potentially long-lasting and harmful to a patient. It is, therefore, crucial that health care providers be aware of the complex relationship between substance abuse, psychotic symptoms, and independent psychotic disorders. This report addresses substance-induced psychosis, by describing those psychotic symptoms most commonly associated with the abuse of specific drugs and alcohol, detailing useful diagnostic techniques and outlining treatment recommendations.

Effects of ozone on epithelium and sensory nerves in the bronchial mucosa of healthy humans.

Neuropeptides released from sensory nerves during inflammation have potent effects on bronchomotor tone, airway secretion, and inflammatory cells. We investigated the effects of ozone on sensory nerves by exposing 12 healthy, nonsmoking subjects to 0.2 ppm ozone and filtered air (FA) for 2 h on separate occasions, with intermittent exercise and rest. Spirometry was performed at baseline and 15 min after exposures, and bronchoscopy (bronchial biopsy and bronchoalveolar lavage [BAL]) was done 6 h after exposure. Frozen sections were immunostained for the anatomic neural marker protein gene peptide (PGP) 9.5 and the sensory neutropeptides substance P (SP) and calcitonin-gene-related peptide (CGRP). Nerves in the submucosa were quantified by image analysis. A trend toward an increase in the levels of polymorphonuclear leukocytes (PMNs) (air versus ozone, median [interquartile range]: 3.5 [2 to 5.3%] versus 9.8 [4.2 to 16.3%], p = 0.07) and ciliated epithelial cells (median [interquartile range]: 1.6 [1.3 to 3.4%] versus 5 [2.2 to 9.8%], p = 0.05) was observed in the BAL fluid (BALF). There was a significant decrease in SP immunoreactivity following ozone exposure (median [interquartile range]: 0.6 [0.05 to 1.2] versus 0.15 [0.08 to 0.18], p < 0.05). A significant inverse correlation was observed between SP immunoreactivity and: (1) percent PMNs and ciliated epithelial cells in the BALF; and (2) percent change in FEV1 following exposure to ozone. These findings indicate that short-term exposure to 0.2 ppm ozone causes epithelial shedding and stimulates subepithelial sensory nerves to release SP into the airways. The release of SP could contribute to bronchoconstriction and subsequent neutrophil infiltration into the airways.

Cocaine abuse and dependence.

Western countries experienced a widespread cocaine epidemic during the 1980s, and the number of frequent users has not declined in this decade. A key factor in the development of this epidemic has been the introduction of "crack," an affordable form of cocaine that appears to be more addicting than the powder. Epidemiologic studies indicate a high incidence of polysubstance abuse among cocaine abusers and probable gender differences in patterns of abuse and response to treatment. An abstinence syndrome has been documented in outpatients after the acute cessation of cocaine; the symptoms perhaps depend on the presence of cues to evoke craving of cocaine and thus are not detected in inpatient settings. Cocaine is a psychostimulant drug that possesses euphorigenic and reinforcing properties. The fact that various animal species self-administer cocaine through the intravenous route provides a reliable animal model for the study of the molecular mechanism of cocaine action and for the characterization of the anatomical substrates responsible for the rewarding properties of the drug. A multisynaptic, allocorticolimbic-accumbens-pallidal circuitry has been identified that seems to play an important role. This pathway may also be part of the neuronal substrates that mediate the reinforcing properties of other classes of abused drugs and, perhaps, motivated behavior in general. Because of this potent reinforcing nature of cocaine in humans, the problem of designing effective therapy for its addiction has not been simply solved. Clinical treatments, guided by animal studies and designed for specific attack of symptoms of the abstinence syndrome, craving and anhedonia, have been tested. To date, only a few agents have proved effective in controlled trials (amantadine, bromocriptine, carbamazepine, and desipramine) and these have limitations of side effects or delayed onset of action. Agents that interact with specific subcomponents of the dopamine system or its connections offer promise for the development of successful agents to treat cocaine abuse and craving in humans.

Tracheobronchomegaly: an unusual presentation of a rare condition.

Tracheobronchomegaly is a rare cause of recurrent chest infections often with persistent, unproductive cough. A case is described which presented as a severe life threatening pneumonia in which the bronchoscopic, radiographic, and computed tomographic findings are given.

The effects of lisuride on mood and sleep during acute withdrawal in stimulant abusers: a preliminary report.

Psychostimulant abusers often experience anhedonia, depression, fatigue, craving, and hypersomnia and increased propensity for rapid eye movement (REM) sleep during periods of acute and subacute withdrawal from cocaine and amphetamine. These signs and symptoms may reflect a state of relative functional dopamine depletion in the brain during abstinence. Lisuride, which has dopaminergic agonist effects, has been reported to reduce signs of psychostimulant withdrawal in rodent models of stimulant abuse. These observations prompted us to test the effects of oral administration of lisuride for 3 weeks (up to 4.0 mg daily) on mood and craving ratings in a double-blind, parallel design, controlled study in hospitalized stimulant abusers during acute withdrawal from cocaine or amphetamine. Although administration of lisuride significantly prolonged REM latency and reduced REM time, amelioration of other signs of withdrawal was not significantly greater in lisuride as compared with placebo treated patients. Self-rated craving ratings, however, were low in both groups throughout the hospital stay. Further studies, perhaps in patients with more severe symptoms during withdrawal, are needed to fully test the efficacy of lisuride in the treatment of stimulant withdrawal.

Laboratory cultivation of prochloron, a tryptophan auxotroph.

Laboratory cultures have been established of the didemnid symbiont Prochloron, a unique prokaryotic alga that synthesizes chlorophylls a and b but no phycobilin pigments. Cell division in Prochloron cultures occurs under acidic conditions (pH 5.5) in the presence of tryptophan. The alga is a naturally occurring tryptophan auxotroph that survives in nature by close association with the host, Diplosoma similis. The metabolic dysfunction that renders Prochloron auxotrophic may involve only the initial step of the tryptophan biosynthetic pathway.

Sterol patterns of cultured zooxanthellae isolated from marine invertebrates: Synthesis of gorgosterol and 23-desmethylgorgosterol by aposymbiotic algae.

QUANTITATIVE STEROL COMPOSITIONS OF CULTURED ZOOXANTHELLAE ISOLATED FROM VARIOUS PACIFIC AND ATLANTIC INVERTEBRATE HOSTS: Zoanthus sociatus (a zoanthid), Oculina diffusa (a scleractian coral), Tridacna gigas (a giant clam), Melibe pilosa (a nudibranch), and Aiptasia pulchella (a sea anemone) are reported. The results clearly demonstrate large differences in sterol patterns of zooxanthellae and that there is no obvious relationship between the taxonomic affiliation of the host and the sterol pattern of its isolated symbiont. The sterols of the zooxanthellae of O. diffusa (Cnidaria) and T. gigas (Mollusca) are qualitatively equivalent. Based on the structures of the two major free sterols synthesized by each alga, the zooxanthellae from different hosts were separated into three distinct groups. It was also found that an aposymbiotic alga can synthesize the unique marine sterols gorgosterol and 23-desmethylgorgosterol. Most of the sterols were identified by using mass spectroscopy and 360-MHz proton magnetic resonance. Spectroscopic data are reported for four novel sterols-(23,24R)-dimethyl-5alpha-cholest-(22E)-en-3beta-o l, 23-methyl-5alpha-cholest-22E-en-3beta-ol, cholesta-5,14-dien-3beta-ol, and 4alpha-methyl-5alpha-cholesta-8(14)-24-dien-3beta-ol.

Identification of 27-nor-(24R)-24-methylcholesta-5,22-dien-3ß-ol and brassicasterol as the major sterols of the marine dinoflagellateGymnodinium simplex.

The major 4α-monomethyl sterol of the dinoflagellateGymnodinium simplex was identified as (24S)-4α,24- dimethylcholestan-3ß-ol. The major 4-demethyl sterols were characterized as (24R)-24-methylcholesta-5,22-dien-3ß-ol (brassicasterol) and 27-nor-(24R)-24-methylcholesta-5,22-dien-3ß-ol. The latter sterol has the opposite configuration at C-24 to that assigned to occelasterol, which has the same basic structure and has previously been reported as a constituent of the sterols of a marine worm. 24-Nor-cholesta-5,22-dien-3ß-ol was also identified along with several other trace sterols. The co-occurrence of 27-nor-(24R)-cholesta-5,22-dien-3ß-ol together with 24-nor-cholesta-5,22-dien-3ß-ol and brassicasterol provides new evidence for the biosynthetic origins of the two former nor-sterols. It is suggested that they may be produced de novo by a route involving nor-isoprenoid pyrophosphates and nor-squalene as intermediates, rather than as bacterial degradation products of brassicasterol (or related sterols) as previously suggested in the literature.

Supramolecular structure of stacked and unstacked regions of the photosynthetic membranes of Prochloron sp., a prokaryote.

Freeze-fracture replicas of the photosynthetic prokaryote Prochloron sp., collected at Coconut Island, Hawaii, show that the thylakoids are differentiated into stacked and unstacked regions much like the thylakoids of green algae and higher plants. On the exoplasmic (E) fracture face, the particle density is greater in stacked regions ( approximately 3100 particles/mum(2)) than in unstacked regions ( approximately 925 particles/mum(2)). On the complementary protoplasmic (P) fracture face, the particle density is lower in stacked regions ( approximately 2265 particles/mum(2) than in unstacked regions ( approximately 4980 particles/mum(2)). The histogram of the diameters of E face particles in unstacked regions shows a single broad peak centered at 80 A. In stacked regions, four distinct peaks, at 75, 105, 130, and 160 A, are observed. These size classes are virtually identical to those found on E faces of thylakoids of the green alga Chlamydomonas and of greening pea chloroplasts. In the latter systems, the different size classes of E face particles are believed to represent photosystem II units surrounded by variable amounts of chlorophyll a/b light-harvesting complex. We propose that the same interpretation applies to the thylakoids of Prochloron, which contain a similar chlorophyll a/b complex. Our results add to the evidence supporting the view of the chlorophyll a/b complex as both a light-harvesting complex and a membrane adhesion factor. The similarity of the architecture of the thylakoids of Prochloron to that of green algal and plant chloroplasts also provides additional evidence of an evolutionary relationship between Prochloron and the chloroplasts of green plants.

Isolation and Characterization of Carotenoid-rich Lipid Globules from Peridinium foliaceum.

Carotenoid-rich oil globules were isolated from the cytoplasm of the binucleate dinoflagellate, Peridinium foliaceum. These orange globules were collected from ruptured cells by ultracentrifugation on a sucrose density gradient, and checked for purity by electron microscopy. The osmiophilic globules were assayed for lipid (including pigment) and protein content. The lipid to protein ratio was 1.39:1, with a calculated density of the globules of 1.05 grams per cubic centimeter. The lipids were composed of hydrocarbon, wax ester (phytyl ester), triglyceride, and polar (no phospholipid) fractions. The biochemical composition indicated that the globules function as a reservoir of energy-rich components in the cell. Microspectrophotometric observations were consistent with pigment analyses which demonstrated that the globules were carotenoid-rich. In addition to beta-carotene, gamma-carotene, and canthaxanthin, the carotenogenic precursors: phytoene, phytofluence, zeta-carotene and beta-zeacarotene were isolated from the globules. Corrected fluorescence maxima of phytoene and phytofluene in hexane were recorded at 340 and 490 nanometers, respectively. Carotenes constituted 3.3% of the total oil globule lipid. The possibility of an extraplastidic carotenogenic enzyme system in P. foliaceum is discussed.

Photosynthetic unit size, carotenoids, and chlorophyll-protein composition of Prochloron sp., a prokaryotic green alga.

Six samples of the prokaryotic, unicellular algae Prochloron sp., which occur in association with didemnid ascidians, were collected from various localities in the tropical Pacific Ocean, and their pigments and chlorophyll-protein complexes were identified and characterized. No phycobilin pigments were detected in any of the species. Chlorophylls a and b were present in ratios of a/b = 4.4-6.9. The major carotenoids were beta-carotene (70%) and zeaxanthin (20%). Minor carotenoids of one isolate were identified as echinenone, cryptoxanthin, isocryptoxanthin, mutachrome, and trihydroxy-beta-carotene; no epsilon-ring carotenoids were found in any sample. Except for the absence of glycosidic carotenoids, the overall pigment composition is typical of cyanobacteria. A chlorophyll a/b-protein complex was present in Prochloron; it was electrophoretically and spectrally indistinguishable from the light-harvesting chlorophyll a/b-protein of higher plants and green algae. It accounted for 26% (compared to approximately 50% in green plants) of the total chlorophyll; 17% was associated with a P700-chlorophyll a-protein. The photosynthetic unit size of 240 +/- 10 chlorophylls per P700 in Prochloron was about half that of eukaryotic green plants. A model is proposed for the in vivo organization of chlorophyll in Prochloron.