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C Duggan

Publications and source records attributed to C Duggan.

At least 55 records · Page 3Linked to original sources
PubMed1998

Semi-quantitation of urokinase plasminogen activator and its receptor in breast carcinomas by immunocytochemistry.

Urokinase plasminogen activator (uPA) is a serine protease involved in cancer invasion and metastasis. uPA acts in vivo by binding to a membrane receptor known as uPAR. In this study, uPA and uPAR levels were semiquantitated by immunocytochemistry in 36 primary breast carcinomas. Using monoclonal antibody HD-UK 1, uPA was detected both in stromal and in malignant cells. However, the predominant location was in the stromal cells. Using double-staining, cells containing uPA were also found to coexpress either cytokeratin (an epithelial cell marker) or more frequently KP1 (a macrophage/monocyte cell marker). With monoclonal antibody HD-uPAR 13.1, uPAR was localized principally to spindle- or macrophage-like stromal cells, especially when these cells surrounded invasive breast cancer. In contrast, uPAR was only rarely detected in cancer cells and was not detected in normal epithelia surrounding tumour or in areas of adenosis. uPA levels in both stromal and epithelial cells were significantly correlated with those for uPAR. We conclude that both uPA and its receptor are mostly present in stromal cells in invasive breast carcinomas. These results suggest that stromal cells collaborate with malignant cells to mediate metastasis.

Antibodies, Monoclonal↗
PubMed1998

Monitoring of lineage-specific chimaerism allows early prediction of response following donor lymphocyte infusions for relapsed chronic myeloid leukaemia.

Donor lymphocyte infusions (DLI) have been shown to enhance the graft-versus-leukaemia (GVL) effect and induce haematological and molecular remission in patients with relapsed CML following allogeneic bone marrow transplantation (BMT). The potent donor cell-mediated cytolysis following DLI may lead to a short period of aplasia before the re-establishment of donor haematopoiesis. The absence of detectable donor cells in patients prior to DLI infusion may result in permanent aplasia in certain patients. We report on four patients who relapsed 1, 3, 6.5 and 7 years post-BMT for chronic phase CML and were treated with DLI from their original BMT donor. Polymorphic short tandem repeats (STRs) were used to assess haematological chimaerism both prior to and following DLI. At the time of relapse, STR-PCR indicated the presence of donor cells in all four patients, at levels ranging from 1-40%. A clinical and molecular response was seen in 4/4 patients following a short period of cytopenia and all patients remain in clinical remission with a follow-up of 2 months-3 years post-DLI. STR-PCR indicated that a response was occurring during the period of pancytopenia when metaphase analysis was unsuccessful. Lineage-specific analysis of the cellular response to DLI was monitored using STR-PCR of peripheral blood (PB) and bone marrow (BM) lymphocyte-enriched fractions and CD2-positive and -negative T cell fractions. In one patient BM and PB CD34-positive and -negative fractions were also assessed. A change in the ratio of donor:recipient cells in the PB lymphocyte fraction was the earliest molecular indication of an anti-leukaemic response. Subsequent conversion to donor chimaerism occurred in the other lineages and the granulocyte fraction was the last lineage to convert. In conclusion, lineage-specific STR-PCR permits detailed monitoring of subtle changes in donor/recipient cell dynamics in specific lineages following DLI during the crucial pancytopenic phase and may be a useful predictor of haematological response to DLI therapy.

Adult↗
PubMed1998

Psychosocial adaptation of patients and families following bone marrow transplantation: a prospective, longitudinal study.

Using a prospective, repeated measures design, this study investigated the psychosocial functioning of patients and a close relative pre- and post-allogeneic and autologous bone marrow transplantation (BMT). All patients (n = 28) undergoing BMT in a 1 year period, and their relatives, were interviewed 1 week pre-transplant and at 3, 6 and 12 months post-BMT, using quantitative and qualitative measures. Pre-transplant data revealed a high level of anxiety (61% with moderate to severe anxiety), and a low level of depression (14% with moderate to severe depression). Twelve patients died in the study period. For the surviving patients there was a statistically significant improvement in physical, psychological and social functioning. Most relatives (88%) reported considerable psychological distress pre-transplant and at 3 months post-transplant, but this was largely resolved by 12 months post-transplant. Significant correlations between the relative's distress and patient's physical and psychological wellbeing were observed at 3 months post-transplant, but not at the other assessment points. The findings from this study will help in counselling patients and their relatives as to what to expect in the year following BMT.

Adaptation, Psychological↗
PubMed1998

Changing the attitudes of 'tomorrow's doctors' towards mental illness and psychiatry: a comparison of two teaching methods.

The General Medical Council's document 'Tomorrow's Doctors' (1993, GMC, London) recommended major changes in the undergraduate curricula of UK medical schools. In Nottingham, the fourth-year psychiatric attachment became shorter in duration, and interactive, problem-oriented, workshop-based learning replaced lectures. We compared the efficacy of this new teaching style in changing medical students' attitudes towards psychiatry and mental illness with that of old-style, didactic, lecture-based teaching. On the first and last days of their psychiatric attachment, 110 fourth-year-medical students (45 old curriculum; 65 new curriculum) completed two self-administered attitudinal measures: the Attitude to Psychiatry Questionnaire (ATP-30) and the Attitude to Mental Illness Questionnaire (AMI). We found that students had favorable attitudes towards psychiatry and mental illness before the attachment. These attitudes became more positive after the attachment in students from both curricula, with no significant difference between the groups and no gender difference. Students found patient contact rewarding, become more accepting of community care, and had greater appreciation of the therapeutic potential of psychiatric interventions. The interactive, student-centred, problem-oriented teaching of the shortened new curriculum appeared as effective in changing medical student' attitudes as a longer attachment with traditional teaching.

Attitude of Health Personnel↗
PubMed1998

Vitamins A and E serum levels in children and young adults with inflammatory bowel disease: effect of disease activity.

BACKGROUND: Hypovitaminosis and fat-soluble vitamin deficiency have been reported in adults with inflammatory bowel disease (IBD). A prospective study was undertaken to determine the prevalence of low serum levels of vitamins A and E in children and young adults with IBD. METHODS: Clinical information and serum for vitamin levels was gathered prospectively from 61 patients with Crohn's disease, 36 patients with ulcerative colitis, and 23 control subjects. Disease activity and disease location were determined for IBD patients. Serum retinol and alpha-tocopherol levels were determined by high-performance liquid chromatography. RESULTS: The prevalence of hypovitaminosis A (defined as serum vitamin A < 20 micrograms/dl) or hypovitaminosis E (defined as serum vitamin E < 5 mg/l) was 16% in the pediatric IBD population studied. Low vitamin A levels were more common than low vitamin E levels. Serum retinol levels correlated significantly with alpha-tocopherol levels. Hypovitaminosis was significantly more prevalent in the Crohn's disease patients who had active disease, an erythrocyte sedimentation rate of more than 25 mm/hour, or a serum albumin level less than 3 mg/dl. CONCLUSIONS: Children and young adults with active IBD frequently have low serum levels of vitamin A or vitamin E. The severity of disease activity is a better predictor of risk for hypovitaminosis than is nutritional status. Further work is necessary to determine whether the hypovitaminosis seen in children with IBD reflects true deficiency.

Adolescent↗
PubMed1998

Obesity and low-fat diets in pediatrics.

The field of pediatric nutrition continues to advance, with increasing evidence that diets early in life have long-lasting effects on health and disease well into adulthood. Pediatricians and nutritionists have long appreciated the importance of adequate nutrition in infancy for optimal growth and development, but only in recent years has the link between pediatric nutrition and diseases of so-called "adult onset" been realized. Two important topics in the field, obesity and the use of low-fat diets early in life, have been the subject of recent literature, and developments in these areas are summarized. Although the genetic basis for some causes of obesity are becoming clear, reliable assessment and treatment of obese children are still wanting in many cases. The ease with which healthy pediatric diets meet the recommended dietary guidelines for fat intake is also reviewed. Finally, the possibility that changes in federal funding of food assistance programs might have adverse effects on pediatric nutrition is also noted.

Adolescent↗
PubMed1998

Family history as a predictor of poor long-term outcome in depression.

BACKGROUND: We investigated whether family history had prognostic significance in depression in a study which addressed some of the methodological shortcomings of previous studies. METHOD: We collected family history data on a consecutive series of 89 patients admitted with RDC major depression, blind to the outcome of the proband. This comprised 116, 283 and 120 first-degree relatives examined with the SADS-L, FH-RDC and case note data, respectively. The outcome of 74 of these probands (83%), previously categorised into four operationally defined groups, was then examined. RESULTS: A positive family history of severe psychiatric illness (i.e. a relative with a history of either a psychosis, hospitalised depression or suicide) was associated with poor outcome in the proband. This association persisted after controlling for variable family size, age structure and gender. As family history was correlated with neither Kendell's neurotic/psychotic index nor the proband's neuroticism score, an individual with high scores an all three would have a greatly increased chance of having a poor outcome. CONCLUSIONS: A family history of severe psychiatric illness in a first-degree relative may be useful as one of the vulnerability factors for predicting poor long-term outcome in depression.

Adolescent↗
PubMed1998

Urokinase plasminogen activator: a prognostic marker in breast cancer including patients with axillary node-negative disease.

Urokinase plasminogen activator (uPA) is a serine protease causally involved in cancer invasion and metastasis. In this study, high concentrations of uPA in primary breast cancers were independently associated with both a shortened disease-free interval and overall survival. For the disease-free interval as endpoint, uPA was a stronger indicator of outcome than lymph node status, whereas for overall survival, nodal status was stronger than uPA. In patients without metastasis to axillary nodes, uPA was also an independent prognostic marker, using both the disease-free interval and overall survival as end points. In contrast to uPA, neither tumor size nor estrogen receptor status was prognostic in the node-negative patients. Measurement of uPA concentrations might thus be of value in selecting the more aggressive subpopulation of node-negative breast cancer patients that could benefit from adjuvant therapy.

Adult↗
PubMed1997

Complications following percutaneous endoscopic gastrostomy and subsequent catheter replacement in children and young adults.

BACKGROUND: Percutaneous endoscopic gastrostomy has gained wide acceptance for patients who require prolonged tube feeding support. We sought to identify complications and associated risk factors of endoscopic gastrostomy and subsequent catheter replacement in pediatric patients. METHODS: Medical records were reviewed for 137 patients. Odds ratios were calculated for complications related to patient age, weight, weight-for-age Z score, and principal diagnosis. RESULTS: Seventeen patients (12.4%) developed significant complications after gastrostomy: cellulitis occurred in 10 patients (7.3%); other complications included gastrocolic fistula (2), duodenal hematoma (1), complicated pneumoperitoneum (1), necrotizing fasciitis (1), gastric perforation (1), and catheter migration (1). Patients with cancer had significantly greater odds for developing a wound infection, and patients with AIDS had significantly greater odds for total complications. A trend toward increased wound infection was observed in patients with cardiac disease. Age, weight, and weight-for-age Z score were not associated with adverse outcome. Two complications occurred in 85 patients (2.4%) after gastrostomy catheter replacement. CONCLUSIONS: Pediatric patients with cancer and AIDS are at increased risk for complications after endoscopic gastrostomy regardless of age, weight, or nutritional status. Infrequent yet life-threatening complications may occur after replacement of initial gastrostomy catheter.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Plasminogen activator inhibitor type 2 in breast cancer.

The serine protease urokinase plasminogen activator (uPA) is causally involved in cancer invasion and metastasis. Activity of this protease in vivo is controlled principally by two inhibitors, one of which is plasminogen activator inhibitor type 2 (PAI-2). In this study, we show that PAI-2 levels were significantly higher in primary breast carcinomas (n = 152) than benign breast tumours (n = 18). In the primary cancers, PAI-2 levels correlated weakly but significantly with those of uPA and PAI-1, but not with tissue type plasminogen activator (tPA) or uPA receptor (uPAR) levels. Using Northern blotting, mRNA for PAI-2 was found in 28.6% of 49 primary breast cancers. In contrast to findings at the protein level, PAI-2 mRNA levels failed to correlate with those for uPA or PAI-1. After immunocytochemistry with primary cancers, PAI-2 was detected predominantly in the malignant cells of primary carcinomas but was also present in stromal cells. Using the median value as a cut-off point, PAI-2 showed no significant relationship with either disease-free interval or overall survival. However, using an optimum cut-off value, patients with low levels of PAI-2 had a worse outcome than those with a high level. We conclude that, unlike PAI-1, high levels of PAI-2 may be a favourable prognostic marker in breast cancer.

Age Factors↗
PubMed1997

Severe aplastic anaemia in association with a unique constitutional translocation 46,XY,t(6;10)(q13;q22)c.

Severe aplastic anaemia (SAA) is an uncommon disorder which may be associated with several congenital syndromes. However, it has rarely been described in association with a constitutional karyotypic abnormality. The breakpoint of the balanced t(6:10)(q13:q22) translocation described here does not disrupt any currently recognized gene of haemopoietic or stromal importance. This report also highlights the problems inherent in the use of bone marrow transplantation (BMT) for treating multiply transfused aplastic anaemia patients.

Adolescent↗
PubMed1997

Infant nutrition: implication for somatic growth, adult onset diseases, and oral health.

The gold standard for assessing the adequacy of nutrient intake in pediatrics is that diet which promotes optimal growth and development. Thus, it is crucial that our methods for measuring these outcomes be valid, reliable, and widely accepted. A review of the recent medical literature in the field of clinical nutrition indicates that both growth data and dietary standards continue to evolve as more data accrue concerning their applicability in both health and disease. In addition, oral nutrition is clearly a determinant of perhaps the most prevalent infectious disease in pediatrics: dental caries. Research in this field stresses the importance of oral fluoride intake in the prevention of caries, as well as the fact that current efforts at reducing milk-bottle tooth decay are inadequate.

Adult↗
PubMed1997

A family clinic--optimising care for HIV infected children and their families.

A family clinic providing specialist paediatric and adult medical, testing, counselling, and terminal care services for families living with HIV was set up at a paediatric tertiary care hospital in London in 1991. During the first five years, until April 1996, 185 children from 149 families attended, including 119 infected children, of whom 32 have died. Only 5% of mothers were born in the UK; the rest were born in 24 different countries, the majority in sub-Saharan Africa. Less than a quarter of children were cared for by both parents, 61% by mothers alone, and 11% by guardians or foster parents. Of the adult attendees, 76% were women, and more than half were untested when they first attended the clinic. Provision of a family planning service within the family clinic was initiated as a result of women presenting with unplanned pregnancies. Shared care with local clinics is increasing, but with the complexity around the management of paediatric HIV infection, particularly with regard to antiretroviral treatments, there is need for continued specialist input. Coordination among specialist and locally based family services is required to provide flexible, accessible, and up to date care for families living with HIV infection in London.

Adolescent↗