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C Duggan

Publications and source records attributed to C Duggan.

At least 73 records · Page 4Linked to original sources
PubMed1997

Urokinase-type plasminogen activator in colorectal cancer: relationship with clinicopathological features and patient outcome.

Urokinase-type plasminogen activator (u-PA) is a serine protease that has been implicated in cancer invasion and metastasis. We quantitated u-PA levels in normal colorectal mucosa, adenomatous polyps, and colorectal cancers and correlated these levels with clinicopathological features and patient survival. Detergent extracts were prepared from 133 colorectal cancers, 133 corresponding colorectal mucosal samples, and 15 synchronous adenomatous polyps. u-PA levels were determined using an ELISA, and a cancer:normal u-PA ratio was calculated for each case. u-PA levels were higher in cancers than in normal tissues, whereas adenomas had intermediate levels (P < 0.0001). u-PA levels were unrelated to clinical or pathological features. Survival was decreased in patients with a high cancer:normal u-PA ratio (P = 0.007). Multivariate survival analysis of patients undergoing curative surgery confirmed that the u-PA cancer:normal ratio was related to outcome (relative risk, 2.67; P = 0.02) and was independent of tumor stage (relative risk, 2.26; P = 0.03). Our study suggests that a high ratio of cancer to normal mucosal u-PA indicates an increased risk of colorectal cancer progression. Measurement of u-PA may provide useful prognostic information in patients undergoing curative surgery for colorectal cancer. The aggressive behavior of colorectal cancers with a high u-PA ratio suggests that the protease might be a suitable target for the development of therapeutic agents to prevent invasion and metastasis.

Adenocarcinoma↗
PubMed1996

A double-blind clinical trial comparing World Health Organization oral rehydration solution with a reduced osmolarity solution containing equal amounts of sodium and glucose.

OBJECTIVE: To compare the safety and efficacy of an oral rehydration solution (ORS) containing 75 mmol/L of sodium and glucose each with the standard World Health Organization (WHO) ORS among Egyptian children with acute diarrhea. METHODS: One hundred ninety boys, aged 1 to 24 months, who were admitted to the hospital with acute diarrhea and signs of dehydration were randomly assigned to receive either standard ORS (311 mmol/L) or a reduced osmolarity ORS (245 mmol/L). Intake and output were measured every 3 hours. RESULTS: In the group treated with reduced osmolarity ORS, the mean stool output during the rehydration phase was 36% lower (95% confidence interval, 1%, 100%) than in those treated with WHO ORS. The relative risk of vomiting during the rehydration phase was significantly lower in children treated with reduced osmolarity ORS (relative risk, 2.4; 95% confidence interval, 1.2, 4.8). During the maintenance phase, stool output, mean intake of food and ORS, duration of diarrhea, and weight gain were similar in the treatment groups. The relative risk of treatment failure (need for unscheduled administration of intravenous fluids) was significantly increased in children receiving standard WHO ORS (relative risk, 7.9; 95% confidence interval, 1.1, 60.9). The mean serum sodium concentration at 24 hours was significantly lower in children receiving the reduced osmolarity ORS solution (134 +/- 6 mEq/L) than in children receiving the standard WHO ORS (138 +/- 7 mEq/L) (p < 0.001). The relative risk of the development or worsening of hyponatremia was not increased in children given the reduced osmolarity ORS, and urine output was similar in the treatment groups. CONCLUSION: The reduced osmolarity ORS has beneficial effects on the clinical course of acute diarrhea in children by reducing stool output, and the proportion of children with vomiting during the rehydration phase, and by reducing the need for supplemental intravenous therapy. These results provide support for the use of a reduced osmolarity ORS in children with acute noncholera diarrhea.

Acute Disease↗
PubMed1996

Vitamin A status in acute exacerbations of cystic fibrosis.

Vitamin A is an essential nutrient for epithelial cell maintenance and repair, and it is known that infectious stresses may depress plasma vitamin A concentrations. Patients with cystic fibrosis are at risk for vitamin A deficiency because of fat malabsorption as well as for the inflammatory stresses of pulmonary exacerbations of their underlying disease. We therefore hypothesized that acute pulmonary exacerbations of CF would depress plasma retinol concentrations, and that these concentrations would return to baseline values when clinical symptoms improved. We prospectively studied 35 CF patients (mean age: 24.2 y) consecutively admitted with pulmonary exacerbations. Plasma retinol, vitamin E, retinol binding protein (RBP), and C-reactive protein (CRP) concentrations were measured on hospital admission and discharge. Dietary intake was measured by using a semiquantitative food-frequency questionnaire. Regression analysis was used to identify significant clinical and laboratory correlates of retinol concentrations. On admission, mean (+/- SD) concentrations of plasma retinol were 1.14 +/- 0.5 mumol/L compared with 1.70 +/- 0.6 mumol/L on discharge (P = 0.0001). Of 35 subjects, 8 (22.9%) had plasma retinol concentrations considered to be in the deficient range (< 0.70 mumol/L). Concurrently, mean concentrations of plasma RBP increased during hospital admission (from 1.46 to 2.24 mumol/L, P = 0.003), and the mean CRP concentration declined (from 25.7 to 9.8 mg/L, P = 0.002). Significant positive correlations were found between plasma retinol concentrations at admission and age, weight, body mass index, triceps-skinfold-thickness percentile, midupper arm circumference percentile, plasma vitamin E, and RBP concentration, thus suggesting that better-nourished patients had more optimal vitamin A status. At admission, plasma retinol concentrations were negatively correlated with maximum body temperature and CRP concentrations, which indicated that the body's acute-phase response was associated with the depression in retinol concentrations. We conclude that plasma retinol concentrations are depressed in acute pulmonary exacerbations of cystic fibrosis, and that concentrations considered to be in the deficient range are common. Vitamin A metabolism during acute inflammatory stress deserves further study.

Acute Disease↗
PubMed1996

How valid are clinical signs of dehydration in infants?

Our objective was to determine the ability of several clinical signs of dehydration to distinguish among degrees of dehydration in infants with acute diarrhea. The design was a prospective cohort study in a pediatric referral hospital in Cairo, Egypt. Infant boys, 3-18 months old, with a history of acute diarrhea (5 or more watery stools per day for no more than 7 days) were eligible, except those with frank protein-energy malnutrition, serious nongastrointestinal illness, or being exclusively breast-fed. Several clinical signs of dehydration were assessed upon study entry. Subjects were then rehydrated with an oral rehydration solution and fed a standardized diet until diarrhea ceased (no watery or loose stools for 16 h). The main outcome measure was percent body weight gain at rehydration and at resolution of illness. Data from 135 subjects were available for analysis. Average (SD) rehydration phase duration was 5.2 (2.1) h, and average (SD) duration of illness was 54.5 (38) h. Multiple regression analysis selected prolonged skinfold, altered neurologic status, sunken eyes, and dry oral mucosa as the clinical signs that correlated best with percent dehydration (R2 for model 0.244, p < 0.001). Mean weight gain for the two assessment systems was 3.6-3.9% for mild, 4.9-5.3% for moderate, and 9.5-9.8% for severe dehydration. The most valid clinical signs of dehydration include prolonged skinfold, altered neurologic status, sunken eyes, and dry oral mucosa. Children with clinical signs of mild or moderate dehydration have fluid deficits on the order of 3 or 5% body weight, respectively.

Acute Disease↗
PubMed1996

Nutritional support of the pediatric intensive care unit patient.

Nutritional support of the critically ill or postoperative pediatric patient continues to develop as a clinical science in the face of technologic, pharmacologic, and nutritional science advances. For ethical and logistical reasons, however, clinical trials of new technologies and interventions often are performed first in adult subjects, and the pediatric intensivist and nutritionist are thereby left to draw conclusions from this literature. This review summarizes recent developments in the clinical nutrition literature concerning the nutritional care of intensive care unit patients, emphasizing experience with pediatric patients when possible. The central role of estimating energy requirements in the intensive care unit, the development of enteral formulas with nutritional as well as possible immunologic properties, the use of anabolic hormones to attenuate the catabolic response to illness, the concept of "conditionally essential" amino acids, and the propensity to use the parenteral route of nutrition when the enteral route is still available are discussed. Future directions in nutritional support, including the development of nutritional pharmacotherapy, are also considered.

Amino Acids↗
PubMed1996

Urokinase plasminogen activator as a predictor of aggressive disease in breast cancer.

Urokinase plasminogen activator (uPA) is a multifunctional protein involved in both extracellular proteolysis and signal transduction. uPA usually mediates its actions while attached to a membrane-bound receptor, termed uPAR. In this study, uPA and its receptor were measured at both protein and mRNA levels in breast cancer. At both levels, concentrations of uPA were significantly correlated with those for uPAR. uPA levels also correlated significantly with cathepsin B and cathepsin D but not with cathepsin L, MMP-8 or MMP-9 levels. Irrespective of the cut-off point used (e.g., median, tertile or quartile values), uPA was a significant prognostic marker for breast cancer.

Blotting, Northern↗
PubMed1995

Neuroticism: a vulnerability marker for depression evidence from a family study.

INTRODUCTION: We investigated the relationship between depressive illness and personality traits from the Eysenck Personality Inventory (EPI) using data from a family study. METHODS: The first-degree relatives of a series of 89 probands with RDC major depression (MD) were subdivided by their lifetime RDC diagnosis into: (1) relatives recovered from MD (n = 34); (2) never-ill relatives (n = 45). The neuroticism (N) and extraversion (E) scores of these two groups were compared using a multilevel linear model, allowing for potential confounders. The relationship between age of onset and recurrence of MD and N scores in group 1 was also examined. RESULTS: (1) Raised N scores were associated with a past history of major depression. (2) There was no such relationship for E scores. (3) Current depressive symptoms were also associated with an increased N score but this did not explain the relationship between previous major depression and N scores. (4) Recurrent episodes of major depression in the recovered MD relatives were significantly associated with increased N scores. CONCLUSION: These data suggest that raised N may be a vulnerability marker for major depression.

Adult↗
PubMed1995

Urokinase plasminogen activator and urokinase plasminogen activator receptor in breast cancer.

Urokinase plasminogen activator (uPA) is a serine protease involved in cancer invasion and metastasis. uPA mediates its action while attached to a membrane-bound receptor (uPAR). In this investigation we show that uPAR levels correlate with uPA levels in human breast cancers. uPAR levels, however, do not correlate with other components of the plasminogen activator system such as tissue-type plasminogen activator (t-PA), PAI-I or PAI-2. In addition, uPAR levels showed no correlation with tumor size, axillary-node status or estrogen-receptor status. On the basis of an optimum cut-off point, patients with breast cancers containing high levels of uPAR had a worse prognosis than patients with low levels of the receptor. However, as a prognostic marker in breast cancer, uPAR was not as strong as uPA. Our results are consistent with data from model systems suggesting that both uPA and uPAR are necessary for metastasis.

Breast Neoplasms↗
PubMed1995

Malnutrition in hospitalized pediatric patients. Current prevalence.

OBJECTIVE: To document the current prevalence of protein-energy malnutrition compared with that reported from the same institution in 1976. DESIGN: All inpatients of this tertiary-care facility were assessed by anthropometric, laboratory, and clinical nutrition assessment methods in a 1-day cross-sectional survey. The comparison study from 1976 was also a 1-day cross-sectional survey. SETTING: A tertiary-care facility in Boston, Mass. PATIENTS: The entire inpatient population was assessed on a single weekday in September 1992. MAIN OUTCOME MEASURES: Prevalence of acute and chronic malnutrition as judged by anthropometric and laboratory data. Data on demographics, admission classification, underlying disease, route of nutrition, and global nutritional status were also assessed. RESULTS: The prevalence of acute protein-energy malnutrition (weight for height) based on the Waterlow criteria was as follows: severe, 1.3%; moderate, 5.8%; mild, 17.4%; and none, 75.5%. The prevalence of chronic protein-energy malnutrition (height for age) was as follows: severe, 5.1%; moderate, 7.7%; mild, 14.5%; and none, 72.8%. Although the prevalence of acute and chronic protein-energy malnutrition was significantly less in 1992 than in 1976 (P = .03 and P < .001, respectively), the numbers are still alarmingly high. Children younger than 2 years and older than 18 years and those with chronic medical conditions had a higher prevalence of protein-energy malnutrition. Twenty-four percent of patients had a serum albumin level less than 30 g/L, 34.8% had a total lymphocyte count less than 1.5 x 10(9)/L, and 24.9% had a hemoglobin concentration less than 105 g/L. One fourth of all patients were obese (> 120% weight for height), with the greatest prevalence in children aged 2 to 18 years. CONCLUSIONS: Acute and chronic protein-energy malnutrition remains common in hospitalized pediatric patients in the United States. Important risk factors may be underlying chronic disease, periods of normally rapid growth, and recognized need for nutrition intervention.

Acute Disease↗
PubMed1995

Intraoperative enteroscopy in the diagnosis of partial intestinal obstruction in infancy.

We present the case of a 4-month-old infant with a prolonged illness due to an occult intestinal stricture. Diagnosis of the lesion escaped conventional radiologic and surgical methods and required intraoperative enteroscopy. Resection of the stricture lead to prompt clinical improvement. Our patient illustrates a primary diagnostic use of intraoperative enteroscopy in the detection of a partial intraluminal small bowel obstruction. As further experience accumulates with small bowel endoscopy, roles for therapeutic enteroscopy (such as polypectomy, photocoagulation, and perhaps balloon dilatation) will certainly arise. Such endeavors will depend on the continued productive collaboration between members of the surgical and gastroenterological teams.

Diseases in Twins↗
PubMed1995

Assay of matrix metalloproteases types 8 and 9 by ELISA in human breast cancer.

Results from model tumour systems suggest that either increased levels of certain metalloproteases (MMPs) or decreased levels of their inhibitors correlate with metastatic potential. In this study, levels of two MMPs, i.e. MMP-8 and -9, and their inhibitor tissue inhibitor of metalloprotease type 1 (TIMP-1) were measured by enzyme-linked immunosorbent assay in human breast tumours. Levels of MMP-8 and -9 correlated significantly with each other, but neither MMP correlated with urokinase plasminogen activator. Levels of both MMP-8 and -9 were also significantly related to levels of TIMP-1. In contrast, neither MMP correlated with plasminogen activator inhibitor. No relationship was found between MMP-8, MMP-9 or TIMP-1 and either tumour size or metastasis to axillary nodes. MMP-8 and -9 levels were inversely related to levels of oestrogen receptors. MMP-8 but not MMP-9 levels were also inversely correlated with progesterone receptor levels. It is concluded that the assay for MMP-8 and -9 described here will permit the evaluation of these proteases as prognostic markers in cancer.

Biomarkers, Tumor↗
PubMed1995

Medium-term course of disaster victims. A naturalistic follow-up.

BACKGROUND: Our aim was to describe the medium-term course (2-3 years) in a series of victims who had experienced severe trauma. METHOD: We selected a consecutive series of 31 trauma victims and applied a structured clinical schedule (CAPS-2) to their psychiatric evaluations prepared for the court on two separate occasions approximately one year apart. RESULTS: Post-traumatic stress disorder and depression were the commonest diagnoses, occurring in 39% and 16% of the victims respectively when they were first assessed. Most had improved between the assessments and this was especially the case for the re-experiencing of the trauma and over-arousal, but less so for avoidance; 20% of subjects showed no improvement, often being handicapped by secondary psychiatric illness. CONCLUSION: Traumatised victims generally showed recovery in the 2-3 years after the trauma, but this was slow and was not universal.

Adult↗
PubMed1993

Comparative efficacy of rice-based and glucose-based oral rehydration salts plus early reintroduction of food.

The use of oral rehydration salts (ORS) to restore fluid balance in children with diarrhoea is universally accepted. However, there is uncertainty about whether glucose-based ORS or ORS based on precooked rice powder is more effective. In a randomised trial we compared the two types of ORS in children who were given food immediately after completion of rehydration. 460 boys aged 3-18 months, admitted to hospital with acute diarrhoea and signs of dehydration, were randomly assigned to groups receiving rice-based and glucose-based ORS solution (230 to each group). After full rehydration (4-12 h), a weaning food consisting of rice and mixed vegetables was given until the diarrhoea stopped. Continuing losses of liquid stool and vomitus were replaced with the assigned ORS solution. There were no differences between the groups during the rehydration phase in stool volume, volume of ORS solution taken, duration of rehydration phase, or weight gain. However, after initiation of feeding, the glucose-based ORS group had significantly lower stool volumes than the rice-based ORS group (142 [95% CI 117-173] vs 96 [77-120] g/kg); they also took a smaller amount of ORS solution (153 [127-185] vs 111 [90-136] mL/kg) and had a shorter duration of diarrhoea (55 [SD 35] vs 44 [35] h). Glucose-based ORS solution was more effective than rice-based ORS solution for the treatment of diarrhoea in children when feeding with a rice-based diet was started soon after correction of dehydration. These results support the continued recommendation of glucose-based ORS solution as standard therapy for treatment of children with acute diarrhoea and emphasize the importance of resuming feeding as soon as dehydration has been corrected.

Acute Disease↗
PubMed1993

Lung deposition of nebulised pentamidine in children.

BACKGROUND: Nebulised pentamidine is effective for preventing Pneumocystis carinii pneumonia in adults with acquired immunodeficiency syndrome. The nebuliser dose required to produce equivalent lung concentrations of pentamidine in children is unknown. This study was performed to measure pulmonary pentamidine deposition in children and to relate this to age, ventilation pattern, and body size. METHODS: Nebulised pentamidine (50 mg in 6 ml saline) was administered to 12 children (including one with lymphocytic interstitial pneumonitis) and to six adults with human immunodeficiency virus infection using a Respirgard II nebuliser. Technetium-99m labeled colloidal human serum albumin was used as an indirect marker for pentamidine and deposition in the lungs was detected by a gamma camera. RESULTS: Absolute deposition of pentamidine was not related to age, height, weight, spirometry, or ventilation characteristics. Deposition, as a mean (SD) percentage of nebuliser output, was similar in children aged 8-11 years (5.5(2.4)%), teenagers aged 12-15 years (7.2(2.2)%) and adults (7.1(2.6)%). Aerosol concentration within the lungs (% nebuliser output deposited/predicted total lung capacity) was therefore higher in children (1.9(1.5)%/1) and teenagers (1.9(0.7)%/1) than in adults (1.0(0.7%)/1), and was negatively correlated with height (r = -0.69) and weight (r = -0.50). Deposition of aerosol in the region of the large central airways was particularly marked in children. Small reductions in forced expiratory volume in one second and forced vital capacity after treatment did not differ significantly between adults and children and visual analogue scores of subjective adverse effects did not vary with age. CONCLUSIONS: These results suggest that children probably require lower nebuliser pentamidine doses to produce lung pentamidine concentrations equivalent to those found to be effective for preventing P carinii pneumonia in adults using the Respirgard II nebuliser.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Clinical audit of behaviour therapy training of nurses.

In health care training, professional examinations of competence test trainees' knowledge rather than their actual contribution to the improvement of patients' health. Clinical training programmes have the ultimate aim of improving patients' health, but rarely measure their success in attaining it. This paper provides an analysis of the results of clinical outcome for 2,032 patients treated during eight consecutive English National Board 650 courses, in which 68 nurse behaviour therapist trainees were trained at the Maudsley Hospital from 1978-91. The outcome of 668 patients treated in three recent courses (1987-91) is compared with that of 1,384 patients treated in five earlier courses (1978-86). Measures and diagnostic categories were similar over the whole study period. The trainees in 1987-91 achieved a similar health gain for most of their patients as did their counterparts in 1979-86, but this was achieved over a shorter time spent with each patient, and with greater effect in patients diagnosed as obsessive ruminators. These efficiency gains seem to reflect the incorporation into recent training of treatment advances in anxiety disorders.

Behavior Therapy↗