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Biomedical subjects

P M Harrington

Publications and source records attributed to P M Harrington.

7 recordsLinked to original sources

Low immunisation uptake: is the process the problem?

OBJECTIVE: To examine mothers' satisfaction with the process of immunisation and its possible contribution to suboptimal immunisation uptake. DESIGN: In depth interviews with mothers. SETTING: Two Community Care Areas, Dublin city, Ireland. PARTICIPANTS: In depth interviews of 23 mothers of children 1-2 years old, recruited purposively from a birth cohort born in 1994. MAIN RESULTS: Mothers preferred general practice to Health Centre immunisation (11:5) for predominantly emotional compared with practical reasons (4:1). Health Centre immunisation was seen, at times, as unacceptably rough and inhuman. Many mothers experienced severe emotional distress at the prospect of inflicting the pain of immunisation on their babies. The non-empathic stance of some immunising doctors was unacceptable to mothers. They valued attempts by health professionals to acknowledge the pain of immunisation and to engage with their baby. Adverse experiences contributed to deferral of future visits and to defaulting behaviour. CONCLUSIONS: Low empathy mass immunisation in clinic type settings may be unacceptable to mothers in the 1990s, and may in part explain suboptimal uptake in health care systems that use such clinics.

Adult↗

Apparent low immunisation uptake in Dublin: under-performance or under-recording?

Through careful follow-up of a cohort, born March to August 1994, we have recorded the highest ever primary immunisation uptake figures for the Dublin area, with completed uptake for Diphtheria, Tetanus and Oral Polio of 92.1%, Haemophilus influenzae type b of 88.7%, Pertussis of 85.7% and Measles/Mumps/Rubella of 78.1%. Eastern Health Board uptake estimates for the same period are 8.1-21.4% lower. We believe the rigour of our data gathering explains this discrepancy. Evidence is reviewed in support of the hypothesis that Eastern Health Board databases underestimate true immunisation uptake.

Child, Preschool↗

Eotaxin and eotaxin receptor (CCR3) expression in Sephadex particle-induced rat lung inflammation.

The beta chemokine eotaxin is a potent eosinophil activator and chemoattractant. We examined immunohistochemically eotaxin protein expression in a range of normal rat tissues and in rat lung during Sephadex particle-induced pulmonary inflammation. The time course of eotaxin expression in lung at various time points after Sephadex administration was related to the appearance of eosinophils in the bronchoalveolar lavage fluid and tissue distribution of eotaxin receptor (CCR3) positive cells. Results showed that eotaxin protein was constitutively expressed by both lung airway epithelial cells and gut epithelial cells in normal tissues in the absence of inflammation. During Sephadex induced pulmonary inflammation, eotaxin expression increased in alveolar macrophages prior to the major increase in eosinophil numbers which reached a peak at 72 h. The pattern of eotaxin pulmonary expression and the location of CCR3 receptor positive cells suggest a chemoattractant gradient resulting in migration firstly into the tissue and subsequently through the airway epithelium into the airways. Treatment of rats with the glucocorticoid dexamethasone or the immunosuppressant cyclosporin A reduced eosinophil entry into lung tissue and airways but had no apparent effect on eotaxin expression in vivo, indicating that both these drugs inhibit eosinophil recruitment either by an eotaxin-independent mechanism, or by targetting factors that synergise with eotaxin, or an event post eotaxin expression.

Animals↗

Vaccine, yes; injection, no: maternal responses to the introduction of Haemophilus influenzae type b (Hib) vaccine.

We used in-depth interviews with 23 mothers of babies aged 1-2 years to explore their response to the addition of Haemophilus influenzae type b (Hib) vaccine to the primary schedule. Acceptability of the vaccine was principally attributable to maternal perceptions as to the severity of meningitis, with a tendency to overestimate the efficacy of the vaccine. Advice from health professionals and the behaviour of peers contributed to its acceptance. Barriers to the uptake of the vaccine included suspicion regarding the newness of the vaccine, a fear of vaccine overload in such young babies, and the distress of two separate injections. There may be a limit to the number of antigens, and particularly the number of injections, acceptable to mothers.

Attitude↗

The complement regulatory proteins CD46 and CD59, but not CD55, are highly expressed by glandular epithelium of human breast and colorectal tumour tissues.

Three of the proteins protecting cells from autologous lysis by complement are: membrane cofactor protein (MCP; CD46), an inhibitor of the membrane attack complex formation (CD59), and decay accelerating factor (DAF; CD55). We have investigated the expression of these proteins in breast and colorectal carcinoma by immunohistochemistry and immunoblotting of breast tissue for CD46. CD46 was consistently and strongly expressed in the epithelial compartment in 26/28 ductal carcinomas of the breast, 9/9 fibroadenomas, and 9/11 cases of control non-neoplastic breast tissue. CD59 showed a similar degree of expression in the fibroadenomas (9/9), but was less strongly expressed in carcinomatous (22/28) and control (5/11) tissues. In marked contrast, no CD55 expression was detected in tissue from 15 ductal carcinomas. Immunoblotting of breast tissue for CD46 showed the same size of the molecule as for lymphocytes. It had however considerably stronger expression in tumour tissue than in non-neoplastic tissue. CD46 and CD59 were either lacking or only weakly expressed in the epithelial component of control colorectal mucosa: 2/15 and 5/15, respectively. In contrast, tissue samples from colorectal adenocarcinomas showed clear staining for both CD59 (10/18) and, more markedly, CD46 (15/18). There was no association between the pattern or intensity of CD46 and CD59 expression and tumour differentiation. As the complement regulatory proteins CD46 and CD59 are also strongly expressed by trophoblast at the feto-maternal tissue interface, these results support the concept that similar mechanisms are employed both by the genetically dissimilar fetus and certain tumours to evade immune attack by their host.

Adenocarcinoma↗

Separation of bovine X and Y sperm based on surface differences.

Aqueous two-phase partition involving thin-layer counter current distribution (TLCCD) has been used to assess surface heterogeneity of ejaculated bovine sperm. When partitioned in charge-insensitive aqueous two-phase systems, which detect non-charge associated surface properties, the sperm fractionates into two distinct populations. Using a Y-chromosome-specific DNA marker, it has been shown that one of these populations is enriched in Y chromosome bearing sperm. However, this population is not pure--it consists of 80% Y sperm, with the other 20% being X sperm. All the sperm in the original population that had begun to undergo the acrosome reaction were separated into this same peak; the sex chromosome composition of these sperm is unknown. Since the aqueous partition of sperm is based on surface properties these results suggest that two populations of Y sperm exist that have different surface characteristics.

Animals↗

Synthesis and biological activity of acyclic analogues of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid.

The synthesis and biological evaluation of a number of analogues of N-[4-[4-(2,4-diamino-1,6-dihydro-6-oxo-5-pyrimidyl) butyl]benzoyl]-L-glutamic acid (2) (7-DM-DDATHF), an acyclic modification of the novel folate antimetabolite 5,10-dideazatetrahydrofolic acid (DDATHF), are described. The synthetic procedure utilized previously for the synthesis of 2, 15, and 16 was extended to the preparation of analogues modified in the benzoyl region with thiophene and methylene groups replacing the benzene ring (compounds 27a-c) and in the glutamate region with aspartic acid and phenylalanine replacing L-glutamic acid (compounds 36, 37). The 2-amino-4,6-dioxo derivative 33 was obtained from intermediate 30 via a palladium-catalyzed carbon-carbon coupling reaction with diethyl (4-iodobenzoyl)-L-glutamate, followed by reduction and removal of protecting groups with base. Cell culture cytotoxicity studies of all of the above acyclic analogues of DDATHF against CCRF-CEM human lymphoblastic leukemic cells gave IC50s ranging from 0.042 greater than 48 microM. Inhibition and cell culture reversal studies against isolated enzymes suggest the mode of action of these compounds. Compound 2 was only 3-fold less inhibitory toward glycinamide ribonucleotide formyltransferase (GARFT, isolated from L1210 leukemic cells) than DDATHF itself. These acyclic analogues were less efficient substrates for the enzyme folylpolyglutamate synthetase (FPGS) compared with their bicyclic counterparts. Moderate antitumor activity was observed for compound 2 against 6C3HED lymphosarcoma and C3H mammary adenocarcinoma in vivo.

Adenocarcinoma↗