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Biomedical subjects

E McIntyre

Publications and source records attributed to E McIntyre.

At least 19 recordsLinked to original sources

Combinations of the FLT3 inhibitor CEP-701 and chemotherapy synergistically kill infant and childhood MLL-rearranged ALL cells in a sequence-dependent manner.

Mixed lineage leukemia (MLL) rearrangements occur in 80% of infants and 5% of older children with acute lymphoblastic leukemia (ALL). These cases have a poor prognosis with current therapy. The FLT3 kinase is overexpressed and constitutively activated in MLL-rearranged ALL cells. The FLT3 inhibitor CEP-701 selectively kills these cells, but is unlikely to be curative if used as monotherapy. To identify potentially synergistic combination strategies, we studied CEP-701 and six standard chemotherapeutic agents in three sequences of exposure (S1: chemotherapy followed by CEP-701, S2: simultaneous exposure to both; and S3: CEP-701 followed by chemotherapy) using MLL-rearranged ALL cell lines and patient bone marrow samples. MTT cytotoxicity and annexin V binding apoptosis assays were used to assess antileukemic effects. Combination indices (CI) were calculated for each combination (CI<0.9 - synergistic; CI 0.9-1.1 - additive; CI>1.1 - antagonistic). A striking pattern of sequence-dependent synergy was observed: S1 was markedly synergistic (mean CI=0.59+/-0.10), S2 was additive (mean CI=0.99+/-0.09) and S3 was antagonistic (mean CI=1.23+/-0.10). The sequence dependence is attributable to the effect of CEP-701 on cell cycle kinetics, and is mediated specifically by FLT3 inhibition, as these effects are not seen in control cells without activated FLT3.

Antineoplastic Agents↗

Sequential chemotherapy by CHOP and DHAP regimens followed by high-dose therapy with stem cell transplantation induces a high rate of complete response and improves event-free survival in mantle cell lymphoma: a prospective study.

Mantle cell lymphoma (MCL) is a distinct clinico-pathological entity with a poor prognosis. We have conducted a prospective study in patients with MCL to evaluate a therapeutic strategy in which CHOP polychemotherapy was followed by DHAP if CHOP failed to induce complete remission. Responding patients then proceeded to an intensification therapy with autologous peripheral blood stem cell transplantation (APBSCT). Twenty-eight consecutive patients with newly diagnosed aggressive MCL were included. After four cycles of CHOP regimen, two complete responses (CR) were obtained (7%) and 14 (50%), five (18%) and seven (25%) patients achieved partial (PR), minor (MR) and no response, respectively (one patient died from septic complications during CHOP induction). The two patients in CR after CHOP underwent intensification with TBI, high-dose cyclophosphamide-etoposide and APBSCT. The other twenty-five patients received DHAP and in this group a response rate of 92% (21 CR (84%), two PR (8%)) was observed. Two patients had progressive disease. The twenty-three responding patients received high-dose therapy (TAM8 regimen: TBI-cytarabine-melphalan) followed by APBSCT. One of the two partial responding patients achieved CR after TAM8. After a median follow-up of 47.6 months (range, 14-70), seven patients have relapsed. Our data confirm that: (1) CHOP regimen induces a low CR rate in MCL; (2) CHOP plus DHAP appears to be much more efficient and allows a large proportion of patients to proceed to high-dose therapy in CR; (3) consolidation therapy including TBI and high-dose Arac-C followed by APBSCT may improve event-free survival.

Adult↗

Attitudes towards infant feeding among adults in a low socioeconomic community: what social support is there for breastfeeding?

An analysis of the role of social support in influencing breastfeeding in a low socioeconomic area in South Australia was undertaken by examining infant feeding attitudes and experiences of mothers, fathers and grandmothers as well as the general community. A random telephone survey of over 3,400 adults (including a more extensive survey of 373 mothers, fathers and grandmothers in the sample) in this area indicated that there was little support for breastfeeding compared to bottle-feeding with similar barriers to breastfeeding found in all target groups as well as the general community. These included breastfeeding in public, the convenience of bottle-feeding, maternal discomfort of breastfeeding, the support required for breastfeeding, fathers' involvement with feeding, and a mother's previous experience of breastfeeding. Strategies promoting and supporting breastfeeding should address these issues and should be directed at the community in general rather than specific groups within the community.

Adolescent↗

Community attitudes to infant feeding.

A cross-sectional study was designed to describe the social context in which breastfeeding occurs by examining experiences of and attitudes toward infant feeding within the general community. Of the 2500 randomly selected adults who participated in the telephone survey, 61% had been breastfed, the youngest child of 52% of participants (who were also parents) had been mainly breastfed but 58% of babies seen by participants were bottle-fed. The attitudes examined in this survey suggest there was little support for breastfeeding, particularly outside the home. Over 80% of participants agreed that bottle-feeding was more acceptable in public places and 70% agreed there was not always a place to breastfeed when outside the home. In addition, bottle-feeding was considered easier and more convenient indicating the social environment was not very breastfeeding friendly. Interventions to enhance environmental support for breastfeeding need to focus on reducing these barriers so that breastfeeding in public is more acceptable and breastfeeding in general is easier and more convenient.

Bottle Feeding↗

Determinants of infant feeding practices in a low socio-economic area: identifying environmental barriers to breastfeeding.

OBJECTIVE: To identify environmental barriers to breastfeeding. METHOD: Focus groups were conducted with young women, parents-to-be, mothers, fathers and grandmothers in 1996 in northern Adelaide, South Australia (a low socio-economic area). RESULTS: Seven focus groups (4-8 participants per group) were conducted. Breastfeeding was seen as being embarrassing to do in public, and not possible to combine with paid employment. While fathers were not supportive of their partners breastfeeding in public, health professionals were seen as strong advocates of breastfeeding. Bottle feeding was perceived to be more convenient for the mother, more acceptable in public but not as good as breastfeeding for the baby. CONCLUSION: An environmental that enables women to breastfeed is far from being achieved in this low socio-economic area, particularly in relation to breastfeeding in public. IMPLICATIONS: Breastfeeding promotion should have a public health focus, concentrating on creating a supportive breastfeeding environment through a multi strategy approach aimed not just at mothers but also at the community.

Adolescent↗

Breastfeeding in public places.

This study reports the results of a survey of restaurant and shopping center managers concerning breastfeeding in their facilities. Managers from 66 restaurants and 27 shopping centers were interviewed by telephone. One-third of the restaurant managers and 48% of the shopping center managers stated that a mother could breastfeed anywhere in their facility regardless of what other customers might say. The remaining managers would either discourage breastfeeding anywhere in their facility, suggest a mother move to a more secluded area if she wished to breastfeed, or were unsure how they would react. The variability in support for breastfeeding by managers of restaurants and shopping centers will continue to create uncertainty for mothers wishing to breastfeed in these public places.

Attitude to Health↗

Suitability of breastfeeding facilities outside the home: an audit of baby change rooms in shopping centres.

In an attempt to identify and audit breastfeeding facilities (baby care rooms) outside the home, this study considered their presence and suitability for breastfeeding in major shopping centres in a low socio-economic area. Only 48% of the shopping centres had baby care rooms, all of which were located either in or next to toilets and were indicated by a range of symbols and terms. The baby care rooms were audited for breastfeeding suitability using the NMAA (Nursing Mothers' Association of Australia) Baby Care Room criteria as an assessment procedure. Only 43.7% of the baby care rooms met all of the 8 NMAA Baby Care Room criteria. Reliability of this assessment process was moderate with a kappa of 0.52. In reviewing these criteria, it was found that more specific clarification of some of the criteria should be undertaken to improve the assessment process. Mothers need to be reassured if they wish to breastfeed in public places by using baby care rooms, that these rooms are suitable for breastfeeding. If breastfeeding is to be encouraged, since it is a healthy choice, it needs to be an easy choice--easy to do outside the home because there are suitable places to breastfeed.

Breast Feeding↗

Effective breastfeeding support in a general practice.

OBJECTIVE: To determine the effectiveness of a breastfeeding support service attached to a general practice. DESIGN: A lactation consultant (LC) was employed in a general practice in Happy Valley. Adelaide over 12 months to provide an appropriate intervention program of education and support for mothers experiencing problems with breastfeeding. The mothers were asked to evaluate the service via a postal questionnaire. The baseline rates of women in this practice who were solely breastfeeding were determined by a retrospective questionnaire sent to all mothers of the practice whose children were 18 months to 2 1/2 years of age (168 mothers formed this baseline group). There were 119 mothers in the intervention group. RESULTS: There was a high, breastfeeding initiation rate for both baseline (94.6%) and intervention (93.4%) groups. There were significantly higher breastfeeding rates in the intervention group at 24 and 26 weeks (63.3% vs 51.2% at 24 weeks [p = 0.015] and 64.7% vs 50.6% at 26 weeks [p = 0.018]). While there was no significant difference in the total number of breastfeeding problems encountered by either group significantly more mothers from the baseline group suffered from engorgement and/or too much milk. Evaluation of the service indicated a high degree of satisfaction. Over 94% of the mothers found the service friendly, supportive, and useful. CONCLUSIONS: This service provides an effective method for the support and protection of breastfeeding.

Adult↗

Effect of asthma treatment on urinary growth hormone excretion in children.

We measured growth hormone (GH) concentrations in first morning urine samples in 110 prepubertal children to determine whether asthma therapies affected GH secretion. The children with asthma were assigned to two groups depending on their asthma treatments: 1) 16 children with a history of asthma, currently not on any treatment, and 2) asthmatics taking inhaled corticosteroids (n = 37), short-term oral corticosteroids (n = 15), or long-term non-corticosteroidal therapies (n = 19). Results obtained from these children were compared with a control group of healthy prepubertal children (n = 23) without previous or current symptoms of asthma. Five consecutive urine samples were collected from each child, and GH concentrations (corrected for urine creatinine) were determined by an enzyme immunoassay. The mean (+/- SD) urine GH concentration determined in the control group (23 healthy prepubertal children) was 15.6 +/- 8.7 ng/L (1.88 +/- 1.29 ng GH/mmol creatinine). The mean (+/- SD) urine GH concentrations in overnight samples were similar in untreated asthmatics (14.1 +/- 6.1 ng/L) and in the treatment groups (14.1 +/- 7.7 ng/L, inhaled corticosteroids; 16.5 +/- 11.7 ng/L, oral corticosteroids; 15.9 +/- 9.8 ng/L, long-term non-corticosteroidal therapies). Irrespective of the manner of expression of urine GH (ng/L) or after correction for urine creatinine concentration (ng GH/mmol), no significant differences were found in the GH excretion among any of the groups. In this study, the intra-individual coefficient of variation for urine GH, expressed as ng/L, ranged between 11 and 87% (median, 32%). When the urine GH was expressed as ng GH/mmol creatinine, the coefficient of variation ranged between 12 and 92% (median, 35%), accounting for approximately 60% of the inter-individual coefficient of variation (mean CV, 56%) and 47% when the urine GH is expressed as ng GH/mmol creatinine. We were unable to determine any short-term differences in urine GH excretion between non-asthmatic children and asthmatics treated with inhaled corticosteroids, oral corticosteroids, or bronchodilators. Our results suggest that there is not an adverse effect of current corticosteroid therapies for childhood asthma on GH secretion.

Anti-Asthmatic Agents↗

Improving the breastfeeding knowledge of health professionals.

OBJECTIVE: To determine whether the breastfeeding knowledge of health professionals can be improved by attending breastfeeding workshops. DESIGN: Health professionals attending a series of two breastfeeding workshops in 1994/1995 were asked to complete the same breastfeeding knowledge questionnaire before and again after the workshops. Issues raised in the questionnaire were discussed during the workshops. These workshops were designed to meet the needs of the attendees, were small in size to encourage active participation, and were based primarily on case studies. SETTING: Health professionals working with mothers and babies in the southern metropolitan area of Adelaide. RESULTS: There was a significant improvement in breastfeeding knowledge in the 65 health professionals who attended both workshops and completed both questionnaires (p < 0.001). CONCLUSIONS: Breastfeeding workshops of the format used are an effective way of improving breastfeeding knowledge in health professionals.

Adult↗

Symptomatic hypocalcemia after intravenous pamidronate.

A 65-year-old woman admitted for palliative care of metastatic renal/bladder carcinoma developed symptomatic hypocalcemia nine days following a single dose of pamidronate. This may have implications for management of patients following discharge from hospital.

Aged↗

Analysis of VH gene expression in CD5+ and CD5- B-cell chronic lymphocytic leukemia.

In contrast to highly mutated follicular lymphomas and multiple myelomas, chronic lymphocytic leukemias (CLLs) frequently express VH genes in germline configuration. It is currently unclear whether this difference is related to the expression of CD5 or to the differentiation stage of the B cell when malignant transformation occurs. We have studied the VH sequence of 11 cases of CD5- B-CLL to address the question whether CD5- B-CLL are derived from naive pregerminal B cells (low mutation pattern) or from germinal center-derived memory B cells (high mutation pattern). Among the 12 detected rearrangements (2 distinct rearrangements in 1 case) VH1 family was found in 2, VH2 in 2, VH3 in 4, and VH4 in 4. Nine different VH genes were detected among the 12 rearrangements, including 2 cases expressing V1-69 (51p1) and 1 case expressing V4-39 (VH4.18), previously reported to be overexpressed in CD5+ B-CLL. A higher mutation pattern, following a random distribution, was observed when compared with classical CD5+ B-CLL. However, as reported in normal B cells, these results appeared to be related to membrane Ig phenotype (less mutations in membrane mu delta-expressing forms in leukemias expressing exclusively membrane mu). Overall, the differences found when comparing the mutational profile with classical CD5+ B-CLL were not clearcut and might be explained more by the membrane isotype (mu v mu delta) than by CD5 expression.

Aged↗

[15O]H2O, [15O]O2 and [15O]CO gas production, monitoring and quality control system.

The 15O gas production system selects the gas production mode, monitors gas delivery conditions and performs quality control needed during the production and delivery of continuous flow radioactive gas for equilibrium and bolus PET studies. Target gas switches choose the appropriate valve positioning for [15O]H2O, [15O]O2 or [15O]CO production while flow rate, pressure and radioactivity are constantly monitored. The system also includes an IBM PC interfaced gas chromatograph which provides chemical and radiochemical quality control by on-line, real time, gas sampling of the delivery line.

Carbon Monoxide↗