Seasonal Inactivated Influenza Vaccination in Oncology Settings

Aims The aims of this study were to establish the uptake rate of seasonal influenza vaccine amongst oncology healthcare workers (HCWs) during the 2016/17 influenza season and to ascertain which factors were associated with or predicted vaccination, along with determining if national guidance regarding influenza vaccination for cancer patients is implemented. Methods A national cross-sectional study was carried out on clinical staff working in oncology day wards. Results Vaccine uptake during the 2016/17 season among oncology day ward staff was 48%. Fear of vaccine side-effects, believing that if one is healthy, there is no need for vaccination, and doubt about vaccine effectiveness negatively predicted vaccination. Most staff (87.6%) recommend vaccination to some or all patients. Conclusion Every effort should be made to ensure HCWs are given the opportunity to get vaccinated, provided with evidence of vaccine effectiveness and safety and empowered to recommend influenza vaccination to their patients.

An ex vivo model using human osteoarthritic cartilage demonstrates the release of bioactive insulin-like growth factor-1 from a collagen-glycosaminoglycan scaffold.

Biomimetic scaffolds hold great promise for therapeutic repair of cartilage, but although most scaffolds are tested with cells in vitro, there are very few ex vivo models (EVMs) where adult cartilage and scaffolds are co-cultured to optimize their interaction prior to in vivo studies. This study describes a simple, non-compressive method that is applicable to mammalian or human cartilage and provides a reasonable throughput of samples. Rings of full-depth articular cartilage slices were derived from human donors undergoing knee replacement for osteoarthritis and a 3 mm core of a collagen/glycosaminoglycan biomimetic scaffold (Tigenix, UK) inserted to create the EVM. Adult osteoarthritis chondrocytes were seeded into the scaffold and cultures maintained for up to 30 days. Ex vivo models were stable throughout experiments, and cells remained viable. Chondrocytes seeded into the EVM attached throughout the scaffold and in contact with the cartilage explants. Cell migration and deposition of extracellular matrix proteins in the scaffold was enhanced by growth factors particularly if the scaffold was preloaded with growth factors. This study demonstrates that the EVM represents a suitable model that has potential for testing a range of therapeutic parameters such as numbers/types of cell, growth factors or therapeutic drugs before progressing to costly pre-clinical trials.

Cancer incidence and mortality due to alcohol: an analysis of 10-year data.

Alcohol consumption is causally related to cancer of the upper aero-digestive tract, liver, colon, rectum, female breast and pancreas. The dose response relationship varies for each site. We calculated Ireland's cancer incidence and mortality attributable to alcohol over a 10-year period. Between 2001 and 2010, 4,585 (4.7%) male and 4,593 (4.2%) female invasive cancer diagnoses were attributable to alcohol. The greatest risk was for the upper aero-digestive tract where 2,961 (52.9%) of these cancers in males and 866 (35.2%) in females were attributable to alcohol. Between 2001 and 2010, 2,823 (6.7%) of male cancer deaths and 1,700 (4.6%) of female cancer deaths were attributable to alcohol. Every year approximately 900 new cancers and 500 cancer deaths are attributable to alcohol. Alcohol is a major cause of cancer after smoking, obesity and physical inactivity. Public awareness of risk must improve. Over half of alcohol related cancers are preventable by adhering to Department of Health alcohol consumption guidelines.

Epidemiology of hepetitis C infection, ERHA/HSE Eastern region.

Hepatitis C became statutorily notifiable in Ireland on 1 January 2004. Prior to 2004, only hepatitis A and hepatitis B were notifiable as distinct types of hepatitis. A third category notifiable under the Infectious Diseases Regulations 1981 was "viral hepatitis unspecified". The majority of cases notified under this heading were thought to be due to infection with hepatitis C Virus (HCV). Between January 1 2004 and December 31 2005, the Department of Public Health HSE Eastern Region, received notification of 2,014 cases of HCV infection (2004, 941 cases, 2005 1,073 cases). This report outlines basic demographic details on cases notified and comments on missing data. Peak age band at notification for males and females is in the 25-29 year old age group where 538 (26.7%) were notified. Thirty cases notified (1.5%) were under 15 years of age. Drug misuse has been confirmed as a risk factor for 1247 (61.9%) of cases notified, and may be a risk factor in a large percentage of the reminder where risk factor data are unknown. Problems with completeness of notification have been identified. Enhanced surveillance of all hepatitis C infections is a prerequisite for future service planning.

HIV infection among heroin users and area of residence.

The aim of this study was to develop a hypothesis to explain the link between HIV prevalence and area of residence. The study was conducted in two parts using two existing data sources. In Part 1, the bloodborne viral test status and test results of a sample of clients attending treatment in December 2001 in two areas of Dublin, an inner city area (Dublin 8) and a suburban area (Dublin 24), were extracted from the Bloodborne Viral Status Dataset created by Grogan. In Part 2 the characteristics of heroin users seeking treatment for the first time at treatment services in their respective areas of residence, Dublin 8 or Dublin 24, between 1997 and 2000 were examined, using data from the National Drug Treatment Reporting System. A higher proportion of heroin users in Dublin 8 had HIV and hepatitis C than did their counterparts in Dublin 24. The analysis suggests that heroin users in Dublin 8 were more likely both to have ever used cocaine and to have used heroin daily, than were those who lived in Dublin 24. Also, a higher proportion of injectors living in Dublin 8 used heroin and cocaine concurrently than did their counterparts in Dublin 24. In both samples, heroin users who lived in Dublin 8 were older than those who lived in Dublin 24. The findings led to a hypothesis:'The risk of acquiring HIV is associated with area of residence and may be linked to cocaine use.

Prevention of breast cancer in the rat with 9-cis-retinoic acid as a single agent and in combination with tamoxifen.

We show that 9-cis-retinoic acid (9cRA) is a potent inhibitor of mammary carcinogenesis induced by N-nitroso-N-methylurea in Sprague-Dawley rats. Rats were first treated with a single dose of N-nitroso-N-methylurea (50 mg/kg body weight) and then fed non-toxic levels of 9cRA (120 or 60 mg/kg of diet). 9cRA was highly effective in reducing tumor incidence, average number of tumors per rat, and average tumor burden, as well as extending tumor latency. The combination of 9cRA with low levels of tamoxifen (TAM; fed at either 1.0 or 0.5 mg/kg of diet) was particularly effective; addition of 9cRA to a TAM regimen doubled the number of animals that were tumor-free at autopsy and significantly diminished tumor number and tumor burden. For suppression of carcinogenesis in vivo, 9cRA was much more potent than all-trans-retinoic acid, both as a single agent or in combination with TAM, although both retinoids had equivalent inhibitory effects on DNA synthesis in cultured human breast cancer cell lines. Both 9cRA and all-trans-retinoic acid induce the expression of the adhesion molecule, E-cadherin, in the SK-BR-3 cell line. We suggest that clinical evaluation of the combination of 9cRA and TAM, either for chemoprevention or for adjuvant therapy, should be considered.

1 alpha,25-Dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531), a new deltanoid (vitamin D analogue) for prevention of breast cancer in the rat.

We have used the vitamin D analogue, 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalcifero l (Ro24-5531), for inhibition of mammary carcinogenesis induced by N-nitroso-N-methylurea (NMU) in Sprague-Dawley rats. Rats were first treated with a single dose of either 15 or 50 mg/kg body weight NMU and then fed Ro24-5531 (2.5 or 1.25 nmol/kg of diet) for 5-7 months. Ro24-5531 significantly extended tumor latency and lessened tumor incidence as well as tumor number in rats treated with the lower dose of NMU. In rats treated with the higher dose of NMU, Ro24-5531 was fed in combination with tamoxifen; in these experiments, Ro24-5531 significantly enhanced the ability of tamoxifen to reduce total tumor burden, as well as to increase the probability that an animal would be tumor free at the end of the experiment. In vitro, Ro24-5531 was 10-100 times more potent than 1,25-dihydroxyvitamin D3 for inhibition of proliferation of human breast cancer cell lines as well as primary cultures of cells from 2 patients with acute myelogenous leukemia. When fed chronically, Ro24-5531 did not elevate serum calcium in the present studies. We propose the new term, "deltanoids," for the set of molecules composed of vitamin D and its synthetic analogues, in a manner similar to the naming of "retinoids" for the corresponding set of molecules related to vitamin A.

N-(4-Hydroxyphenyl)retinamide, a new retinoid for prevention of breast cancer in the rat.

The synethesis of a new retinoid, N-(4-hydroxyphenyl)-all-trans-retinamide, which has useful biological properties, is described. This retinoid was more potent than retinyl acetate in reversing keratinization caused by retinoid deficiency in tracheal organ culture. It was markedly less toxic than retinyl acetate when fed p.o. to rats over 2-week or 6-month periods. It was an effective agent for inhibition of the development of breast cancer induced in rats by N-nitroso-N-methylurea, although it was not as potent as retinyl acetate in this regard. However, the lesser toxicity of 4-hydroxyphenylretinamide makes it a superior agent for prevention of breast cancer. High-pressure liquid chromatographic analyses of liver and breast extracts from rats treated for 6 months with retinoids show the pharmacokinetic basis for the superiority of 4-hydroxyphenylretinamide; this retinoid and its metabolites were found in high concentrations in breast tissue, without any measurable accumulation in the liver or evident liver toxicity. In contrast, chronic feeding of retinyl acetate caused marked deposition of retinyl esters in the liver and severe hepatotoxicity. Whole mounts of rat mammary glands, made after chronic feeding of 4-hydroxyphenylretinamide, showed that it had a marked antiproliferative effect on mammary epithelium.

Adipokinetic hormone and the immune responses of locusts to infection.

Injections of Bacillus, or of blastospores from the entomopathogenic fungus, Metarhizium anisopliae, activate the prophenoloxidase (PPO) cascade, and coinjection of adipokinetic hormone-I (AKH) enhances and prolongs these responses. When injected concurrently with an immunizing dose of live bacteria, AKH suppresses the appearance of antimicrobial activity and, after a short delay, increases the growth of bacteria within the hemocoel. Injections of live Escherichia coli or Pseudomonas aeruginosa into locusts fail to activate PPO in the hemolymph, even when coinjected with AKH. The coinjection of bacteria and hormone is rarely lethal to the locust. However, if locusts are injected with AKH when they are infected with Metarhizium, they die more rapidly than if no AKH is administered.

Psychometric study of patient knowledge test.

The results of a psychometric study of the Test of Patient Knowledge are reported. The 50-item, multiple-choice test, developed by Etzwiler and associates at the International Diabetes Center, consists of a total score and seven subscores based on seven nonoverlapping content categories: nutrition, insulin, general knowledge, methods of control, pattern control, exercise, and complications. The results described herein provide evidence for the validity of the test (content, concurrent, and discriminant validity), a high level of reliability (Cronbach's alpha = .88), readability for the layperson at the 7th- to 8th-grade level, and sensitivity to instructional gains. The literature on psychometric research with other tests of patient knowledge of diabetes is reviewed and compared with the results of this study.

Long-term follow-up of women with breast cancer: rationale for policy change.

BACKGROUND: The number of breast cancer survivors in our ageing population continues to rise. Policy makers internationally are seeking to identify alternatives to follow-up care in an acute setting. AIMS: The National Cancer Control Programme set out to develop a new policy for long-term follow-up of breast cancer survivors in Ireland. METHODS: Policy development was informed by analysis of current attendances at breast surgical clinics for routine follow-up, extraction of the necessary components of follow-up from international guidelines and focus group research with Irish patients. RESULTS: Intensive follow-up investigations, other than mammography, do not confer additional survival benefit or improved quality of life. Provision of routine follow-up care of breast cancer survivors by GPs has been shown to be equivalent to follow-up by specialist clinics, in terms of clinical outcomes, patient quality of life and patient satisfaction. In Ireland, routine follow-up accounted for 15.4% (95% CI: 13.8-17.0%) of clinic appointments. A third were at least 5 years post-operative. Women highlighted issues such as attachment to specialist services, importance of communication and need for clarity as to where responsibility of care lies. Reassurance, confidence in the primary care practitioner, and coordination of multiple appointments were also identified as important issues. CONCLUSION: A significant proportion of breast cancer survivors attending hospital surgical clinics for long-term follow-up could be safely discharged at 5 years, with the hospital maintaining responsibility for annual mammography. Successful implementation will depend on informed patients, clinicians' acceptance and communication between primary and secondary care.

Left hemispheric activation in depersonalization disorder: a case report.

Depersonalization disorder is classified in DSM-III-R (APA 1987) as a dissociative disorder characterized by altered perception or experience of the self. To date, there are no known reports of the neurobiological features of this disorder. We report clinical and biological correlates in a patient with depersonalization disorder previously unresponsive to a variety of anticonvulsant, monoamine oxidase inhibitor, and tricyclic antidepressant trials, but for whom fluoxetine partially reduced depersonalization symptoms, but not associated anxiety and depression. Neurophysiological, neuroanatomical and neuropsychological findings revealed left hemispheric frontal-temporal activation and decreased left caudate perfusion. These findings suggest a similarity to the neuropsychiatric data reported in obsessive-compulsive disorder patients.

Effects of dietary zinc depletion on seminal volume and zinc loss, serum testosterone concentrations, and sperm morphology in young men.

Identification of the andrological variables most sensitive to zinc depletion would expedite the diagnosis of male reproductive pathology induced by zinc deficiency. Eleven volunteers living on a metabolic ward were fed a diet composed of a mixture of a semisynthetic formula and conventional foods supplemented with ZnSO4 to supply a total of 1.4, 2.5, 3.4, 4.4, or 10.4 mg Zn/d. After an equilibration period of 28 d (10.4 mg Zn/d), all treatments were presented for 35 d each, the first four in random order and the fifth last. Compared with when they were consuming 10.4 mg Zn/d, volunteers consuming 1.4 mg Zn/d exhibited decreased semen volumes (3.30 vs 2.24 mL) and serum testosterone concentrations (26.9 vs 21.9 nmol/L), and no change in seminal zinc concentrations. Compared with 10.4 mg Zn/d, treatments of 1.4, 2.5, and 3.4 mg Zn/d decreased the total semen zinc loss per ejaculate (6.29 vs 3.81, 4.68, and 5.03 mumols/ejaculate). Seminal loss accounted for 9% of total body zinc loss when 1.4 mg Zn/d was consumed. Seminal phosphorus concentrations were elevated during all four phases of zinc depletion (28.4 vs 32.9, 31.0, 34.2, and 33.6 mmol/L). The findings suggest that serum testosterone concentrations, seminal volume, and total seminal zinc loss per ejaculate are sensitive to short-term zinc depletion in young men.

Ascorbic acid: effect on ongoing iron absorption and status in iron-depleted young women.

The effect of ascorbic acid on iron retention from a diet with predicted low iron bioavailability (containing minimal meat and ascorbic acid) was investigated in iron-depleted premenopausal women. Eleven women were depleted of storage iron (indicated by serum ferritin) through a combination of diet (5.0 mg Fe/2000 kcal for 67-88 d) and phlebotomy. They then consumed a diet containing 13.7 mg Fe/2000 kcal, supplemented with placebo or ascorbic acid three times daily (1500 mg total) with meals for 5.5 wk. Ascorbic acid improved apparent iron absorption (balance method) [38 +/- 2% (means +/- SEM) vs 27 +/- 2%]. Ascorbic acid also improved hemoglobin, erythrocyte protoporphyrins, and serum iron but not hematocrit, serum ferritin, iron-binding capacity, or transferrin saturation. In iron-depleted women consuming a diet with predicted poor iron availability, ascorbic acid supplementation enhanced body iron retention for 5.5 wk.

Homeostatic control of zinc metabolism in men: zinc excretion and balance in men fed diets low in zinc.

Zinc metabolism was studied in 11 men. The study began with 28-d equilibration when dietary zinc was 159 mumol/d (X), followed by 35-d periods when the diet contained 21.9 (I), 37.5 (II), 51.6 (III), or 67.8 (IV) mumol Zn/d in random order, and ended with 35 d with X. The diet was conventional foods and egg white protein. Zinc balance, including surface and semen losses, was zero only during I. Semen zinc was unaffected by diet. Plasma zinc dropped to 0.44 and 0.49 mumol/L in two subjects during I and was significantly decreased during I compared with X (P < 0.0002). Urinary zinc declined with decreasing zinc intake. A combination of urinary and plasma zinc criteria from Baer and King (Am J Clin Nutr 1984; 39:556-70) could be used to distinguish stages of zinc deficiency. By these criteria, no subjects were deficient during IV, one was marginally deficient during III, three were marginally deficient during II, and seven were deficient during I.

North Carolina macular dystrophy phenotype in France maps to the MCDR1 locus.

PURPOSE: To determine if a family in France, which manifests an autosomal dominant macular dystrophy, has North Carolina macular dystrophy (MCDR1) and to determine its possible molecular genetic relationship with the original North Carolina family. METHODS: A family from Northern France with a macular dystrophy underwent comprehensive ophthalmic examinations and were ascertained for genetic studies. Blood collection and examinations were performed on 38 individuals. Fundus photographs with a hand held KOWA camera were obtained on affected subjects. DNA was extracted and genotyping performed using new microsatellite genetic markers, which have recently been found in the MCDR1 (North Carolina macular dystrophy) region. Standard two - point linkage and haplotype analysis was performed. RESULTS: Eleven individuals were found with the clinical manifestations of North Carolina macular dystrophy. Two - point linkage analysis generated a maximum peak LOD score of 4.5 with a recombination of 0% between D6S1717 and the macular dystrophy locus in the French family. The haplotype associated with the disease is, however, different from that of the original North Carolina family. CONCLUSIONS: These findings indicate that the macular dystrophy gene in this French family maps to the same region as that of North Carolina macular dystrophy (MCDR1) locus but that independent mutations are involved. The disease in the French family is clinically and genetically similar to North Carolina macular dystrophy. Therefore MCDR1 occurs in various ethnic groups, is present world-wide, and there remains no evidence of genetic heterogeneity for this clinically distinct form of macular degeneration.

Changes in lipophorins are related to the activation of phenoloxidase in the haemolymph of Locusta migratoria in response to injection of immunogens.

In Locusta migratoria, activation of phenoloxidase in the haemolymph in response to injection of laminarin is age-dependent: being absent in fifth instar nymphs and newly emerged adults, and only becoming evident four days after the final moult. This pattern of change in phenoloxidase activation correlates with the pattern of change in the concentration of apolipophorin-III (apoLp-III) in the haemolymph. Injection of a conspecific adipokinetic hormone (Lom-AKH-I) has no effect on the phenoloxidase response in nymphs or newly emerged adults but, in adults older than four days, co-injection of the hormone with laminarin prolongs the activation of phenoloxidase in the haemolymph: a similar enhancement of the response to laminarin is observed in locusts that have been starved for 48 h but not injected with AKH-I. During most of the fifth stadium, injection of laminarin results in a decrease in the level of prophenoloxidase in the haemolymph; an effect that is not observed in adults of any age. Marked changes in the concentration of apoLp-III, and the formation of LDLp in the haemolymph, are observed after injection of laminarin (or LPS) and these are remarkably similar, at least qualitatively, to those that occur after injection of AKH-I. The involvement of lipophorins in the activation of locust prophenoloxidase in response to immunogens is discussed.

Localization of transforming growth factor-beta isotypes in lesions of the human breast.

Transforming growth factor-beta s (TGF-beta) comprise a highly conserved family of multifunctional cell regulatory peptides that may play a role in a variety of pathologic processes. To date, five TGF-beta isotypes have been identified, three of these in mammalian systems. A number of cultured human breast carcinoma cell lines produce biologically inactive latent TGF-beta and are growth inhibited by activated TGF-beta; TGF-beta production is estrogen-influenced in some of these cell lines. To investigate the potential role of the TGF-beta isotypes in human breast disease, we localized TGF-beta s 1, 2, and 3 immunohistochemically in normal breast, fibrocystic change, epithelial hyperplasia, sclerosing adenosis, fibroadenoma, cystosarcoma phyllodes, and several carcinoma variants. Transforming growth factor-beta s 1, 2, and 3 were identified intracellularly in most active mammary epithelia, regardless of the lesion, including carcinoma; the associated stroma contained little or no intracellular TGF-beta. An antibody that recognizes an extracellular conformation of TGF-beta stained normal intralobular stroma and, more extensively, the stroma of active fibroadenomas and low-grade phyllodes tumors and the desmoplastic stroma of carcinomas. The results indicate the potential for paracrine and autocrine regulation of the mammary gland by TGF-beta and suggest an association between TGF-beta and abnormal stromal proliferations. Altered expression of TGF-beta s 1, 2, and 3 at the protein level in mammary epithelia appears not to be a major feature of most breast lesions, raising the possibility that altered cellular response to the TGF-beta already present may play a role in the development of breast disease.

Obsessive compulsive disorder, depression, and fluoxetine.

BACKGROUND: Fluoxetine, a selective serotonin reuptake blocker, is an antidepressant medication that has also been shown in open clinical trials and one controlled trial to be effective in the treatment of obsessive compulsive disorder (OCD). OCD is often complicated by depression, and depressive symptoms may interfere with response to both pharmacologic and behavioral treatments. METHOD: We describe pilot data from 10 outpatients who met DSM-III-R criteria for OCD in whom the possibility of a depressive reaction or lack of antidepressant response occurred during an open trial of fluoxetine. RESULTS: Rapid increase in fluoxetine dose to high doses was associated with depressive symptoms in 6 patients. In 8 patients, improvement in depression was associated with addition of a tricyclic antidepressant to fluoxetine treatment. In 5 patients, both OCD and depressive symptoms improved when the patient was switched to the partially selective serotonin reuptake blocker clomipramine. CONCLUSION: This paper serves to alert clinicians to the possibility of a depressive reaction, or lack of antidepressant response, to fluoxetine in OCD patients. This possibility can only be resolved scientifically by adequately controlled experimental trials. If depression occurs, combined fluoxetine and tricyclic treatment, or a switch to a partially selective serotonin reuptake inhibitor, may be helpful. Special considerations and side effects of combined fluoxetine-tricyclic treatment are described.