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Biomedical subjects

C Duggan

Publications and source records attributed to C Duggan.

At least 19 recordsLinked to original sources
PubMed2006

The expression of FHIT, PCNA and EGFR in benign and malignant breast lesions.

Immunohistochemical staining for FHIT and PCNA proteins was carried out in 451 breast lesions showing nonproliferative benign breast disease (BBD) (n=263), proliferative BBD without atypia (n=128), proliferative BBD with atypia (n=11), carcinoma in situ (n=15) or invasive carcinoma (n=34) and for EGFR protein in a subset of 71 of these cases. FHIT underexpression was not detected in nonproliferative lesions, but occurred in 2% of proliferative BBD without atypia, 10% proliferative BBD with atypia, 27% of carcinoma in situ and 41% of invasive carcinoma, which suggests that it could be useful in assessing those carcinoma in situ lesions (ductal, DCIS and lobular, LCIS) that are more likely to progress to malignancy. Preliminary microarray comparisons on DCIS and invasive carcinoma samples dissected from formalin-fixed paraffin sections showed a consistent downregulation of two previously identified FHIT-related genes, caspase 1 and BRCA1 in lesions underexpressing FHIT.

Acid Anhydride Hydrolases↗
PubMed2006

Psychological therapies for people with borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is a relatively common personality disorder with a major impact on health services as those affected often present in crisis, often self-harming. OBJECTIVES: To evaluate the effects of psychological interventions for people with borderline personality disorder. SEARCH STRATEGY: We conducted a systematic search of 26 specialist and general bibliographic databases (December 2002) and searched relevant reference lists for further trials. SELECTION CRITERIA: All relevant clinical randomised controlled trials involving psychological treatments for people with BPD. The definition of psychological treatments included behavioural, cognitive-behavioural, psychodynamic and psychoanalytic. DATA COLLECTION AND ANALYSIS: We independently selected, quality assessed and data extracted studies. For binary outcomes we calculated a standard estimation of the risk ratio (RR), its 95% confidence interval (CI), and where possible the number need to help/harm (NNT/H). For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were summated using a weighted mean difference (WMD). MAIN RESULTS: We identified seven studies involving 262 people, and five separate comparisons. Comparing dialectical behaviour therapy (DBT) with treatment as usual studies found no difference for the outcome of still meeting SCID-II criteria for the diagnosis of BPD by six months (n=28, 1 RCT, RR 0.69 CI 0.35 to 1.38) or admission to hospital in previous three months (n=28, 1 RCT, RR 0.77 CI 0.28 to 2.14). Self harm or parasuicide may decrease at 6 to 12 months (n=63, 1 RCT, RR 0.81 CI 0.66 to 0.98, NNT 12 CI 7 to 108). One study detected statistical difference in favour of people receiving DBT compared with those allocated to treatment as usual for average scores of suicidal ideation at 6 months (n=20, MD -15.30 CI -25.46 to -5.14). There was no difference for the outcome of leaving the study early (n=155, 3 RCTs, RR 0.74 CI 0.52 to 1.04). For the outcome of interviewer-assessed alcohol free days, skewed data are reported and tend to favour DBT. When a substance abuse focused DBT was compared with comprehensive validation therapy plus 12-step substance misuse programme no clear differences were found for service outcomes (n=23, 1 RCT, RR imprisoned 1.09 CI 0.64 to 1.87) or leaving the study early (n=23, 1 RCT, RR 7.58 CI 0.44 to 132.08). When dialectical behaviour therapy-oriented treatment is compared with client centred therapy no differences were found for service outcomes (n=24, 1 RCT, RR admitted 0.33 CI 0.08 to 1.33). However, fewer people in the DBT group displayed indicators of parasuicidal behaviour (n=24, RR 0.13 CI 0.02 to 0.85, NNT 2 CI 2 to 11). There were no differences for outcomes of anxiety and depression (n=24, 1 RCT, RR anxiety BAI >/=10 0.60 CI 0.32 to 1.12; RR depression HDRS >/=10 0.43 CI 0.14 to 1.28) but people who received DBT had less general psychiatric severity than those in the control (MD BPRS at 6 months -7.41 CI -13.72 to -1.10). Finally this one relevant study reports skewed data for suicidal ideation with considerably lower scores for people allocated to DBT. When psychoanalytically oriented partial hospitalization was compared with general psychiatric care the former tended to come off best. People who received treatment in a psychoanalytic orientated day hospital were less likely to be admitted into inpatient care when measured at different time points (e.g. n=44, RR admitted to inpatient 24 hour care >18 to 24 months 0.05 CI 0.00 to 0.77, NNT 3 CI 3 to 10) Fewer people in psychoanalytically oriented partial hospitalization needed day hospital intervention in the 18 months after discharge (n=44, 1 RCT, RR 0.04 CI 0.00 to 0.59, NNT 2 CI 2 to 8). More people in the control group took psychotropic medication by the 30 to 36 month follow-up, than those receiving psychoanalytic treatment (n=44, 1 RCT, RR 0.44 CI 0.25 to 0.80, NNT 3 CI 2 to 7). Anxiety and depression scores were generally lower in the psychoanalytically oriented partial hospitalization group (n=44, 1 RCT, RR >/=14 on BDI 0.52 CI 0.34 to 0.80, NNT 3 CI 3 to 6), as are global severity scores. People receiving psychoanalytic care in a day hospital had better social improvement in social adjustment using the SAS-SR at 6 to 12 months compared with people in general psychiatric care (MD -0.70 CI -1.08 to -0.32). Rates of attrition were the same (n=44, 1 RCT, RR leaving the study early 1.00 CI 0.23 to 4.42). AUTHORS' CONCLUSIONS: This review suggests that some of the problems frequently encountered by people with borderline personality disorder may be amenable to talking/behavioural treatments but all therapies remain experimental and the studies are too few and small to inspire full confidence in their results. These findings require replication in larger 'real-world' studies.

Behavior Therapy↗
PubMed2006

Pharmacological interventions for people with borderline personality disorder.

BACKGROUND: Borderline Personality Disorder (BPD) is prevalent (2% in the general population, 20% among psychiatry in-patients) and has a major impact on health facilities as those affected often present in crisis but then make poor use of further attempts to help them. OBJECTIVES: To evaluate the effects of pharmacological interventions for people with borderline personality disorder. SEARCH STRATEGY: We conducted a systematic search of 26 specialist and general bibliographic databases (October 2002) and searched relevant reference lists for further trials. SELECTION CRITERIA: We included all randomised clinical trials comparing any psychoactive drugs with any other treatment for people with borderline personality disorder. DATA COLLECTION AND ANALYSIS: We independently selected, quality assessed and data extracted studies. For binary outcomes we calculated a standard estimation of the risk ratio (RR), its 95% confidence interval (CI), and where possible the number need to help/harm (NNT/H). For continuous outcomes, endpoint data were preferred to change data. Non-skewed data from valid scales were synthesised using a weighted mean difference (WMD). MAIN RESULTS: We found ten small (total n=554), short, randomised studies involving eight comparisons from which we could extract usable data. Studies comparing antidepressants with placebo were small (total n=79, 2 RCTs) but for ratings of anger fluoxetine may offer some improvement for those on antidepressant therapy over placebo (n=22, 1 RCT, RR anger not improved 0.30 CI 0.10 to 0.85, NNT 2 CI 2 to 9). The one small study investigating the important outcome of attempted suicide found no difference between mianserin and placebo (n=38, 1 RCT, RR 0.82 CI 0.44 to 1.54). Haloperidol may be better than antidepressants for symptoms of hostility and psychotism. There were few differences between MAOIs and placebo except that people given MAOIs were less hostile (n=62, 1 RCT, MD -9.19 CI -16.12 to -2.26). Although some ratings were statistically significant the comparison of MAOIs with antipsychotics did not show convincing differences. Antipsychotics may effect some mental state symptoms more effectively than placebo but results are difficult to interpret clinically and there is little evidence of advantage of one antipsychotic over another. Finally mood stabilisers such as divalporex may help mental state (n=16, 1 RCT, RR no improvement in mental state 0.58 CI 0.36 to 0.94, NNT 3 CI 2 to 17) but data are far from conclusive. AUTHORS' CONCLUSIONS: Pharmacological treatment of people with BPD is not based on good evidence from trials and it is arguable that future use of medication should be from within randomised trials. Current trials suggest that the positive effect of antidepressants, in particular, could be considerable. Well designed, conducted and reported clinically meaningful trials are possible and needed with, perhaps, the question of antidepressant versus placebo being addressed first.

Antidepressive Agents↗
PubMed2005

Temporal reliability of psychological assessments for patients in a special hospital with severe personality disorder: a preliminary note.

BACKGROUND: The new programme for assessing those with dangerous and severe personality disorder relies heavily on psychological assessments of personality disorder and risk. METHODS: The temporal reliability of assessments of psychopathy (PCL-R), risk (HCR-20) and personality was assessed using the International Personality Disorder Examination (IPDE) in 15 randomly selected male prisoners in a high secure hospital carried out at intervals varying between a mean of nine and 19 months after initial assessments by a variety of assessors. RESULTS: Using the intra-class correlation coefficient the agreement varied between 0.57 (HCR-20), 0.58 (PCL-R) and 0.38-0.70 for IPDE personality disorders, with the best agreement for antisocial personality disorder (0.70). COMMENT: These levels of agreement are consistent with other recent work on temporal reliability of personality instruments but are a little too low for confidence in these measures alone in the assessment process.

Adult↗
PubMed2004

Assessing the pharmaceutical care needs of asthmatic patients.

OBJECTIVES: To measure patients' perceptions of their care needs, by developing a tool to assess these needs and evaluate its utility in community pharmacy practice. METHOD: A survey tool comprising 37 items was developed to assess asthmatic patients' perceptions of their health-related needs, using data from literature reviews and expert opinions. The tool was piloted on 25 patients to ensure the content of the questionnaire was valid. Changes were made following piloting and the modified tool was then tested in the main study, on 101 patients from thirteen community pharmacies in Portugal. Data from this phase were subjected to factor analysis and reliability testing. RESULTS: 118 asthmatic patients were recruited, of which 101 questionnaires were eligible for analysis. From these, 40 were male (39.6%) and 61 were female (60.4%). The mean age of respondents was 41 years (sd = 19.02). The first changes made to the survey tool included the adding of items relevant to patients recruited in the pilot and the simplification of the scaling used. The survey tool was then subjected to factor analysis and reliability testing. Six scales emerged, which described the need for GP support, specialist support, pharmacist support, nurse support, other carers' support and written support. Internal consistency was good (Cronbach's coefficient alpha ranged from 0.81 to 0.93). Although there were no significant associations between educational level and other factors, other attributes influenced the communication between pharmacist and physician (chi2 = 6.972; P = 0.031). Patients with a lower level of education (up to six years) valued communication between these two professionals more than among patients with higher education. The patient's age group was associated with an expressed need for explanation of inhaler technique (chi2 = 6.494; P = 0.039). There was extended need in both oldest and youngest patients. There was a significant difference between high and low scorers to the factor 'pharmacist's role in asthma' (F1) and patients treated by either specialist or GP (chi2 = 4.935; P = 0.026). There were differences between those who were bothered by their asthma or not and their perceptions of 'Pharmacist's ideal role in asthma' (F1 & 3) (chi2 = 5.967; P = 0.051). CONCLUSION: The tool needs further development to ensure its validity and utility in practice. This will provide greater insight into patients' perceptions of their healthcare needs, which can allow health professionals to target their interventions. Such a tool may then be used in pharmacies that intend to change their current practice, to raise pharmacists' awareness of patients' demands. Developing ways to meet those needs will ultimately lead to an increased quality service and therefore 'client' satisfaction.

Adult↗
PubMed2004

The urokinase plasminogen activator system: a rich source of tumour markers for the individualised management of patients with cancer.

The urokinase plasminogen activator (uPA) system consists of the serine protease uPA, the glycolipid-anchored receptor, uPAR, and the 2 serpin inhibitors, plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2). Recent findings suggest that uPA, uPAR and PAI-1 play a critical role in cancer invasion and metastasis. Consistent with their role in cancer dissemination, high levels of uPA, PAI-1 and uPAR in multiple cancer types correlate with adverse patient outcome. The prognostic value of uPA/PAI-1 in axillary node-negative breast cancer patients was recently validated using both a prospective randomised trial and a pooled analysis. Assay of uPA and PAI-1 may thus help identify low-risk node-negative patients for whom adjuvant chemotherapy is unnecessary. Finally, emerging data suggest that high levels of uPA and PAI-1 in breast cancer are associated with a preferential response to adjuvant chemotherapy but relative resistance to hormone therapy. The measurement of uPA components, especially in breast cancer, thus has the potential to help with individualised patient management.

Biomarkers, Tumor↗
PubMed2004

Ultrase MT12 and Ultrase MT20 in the treatment of exocrine pancreatic insufficiency in cystic fibrosis: safety and efficacy.

BACKGROUND: Cystic fibrosis causes exocrine pancreatic insufficiency, leading to malabsorption. Supplemental pancreatic enzyme therapy alleviates the concomitant malnutrition experienced by cystic fibrosis patients. It is recognized that patients experience variations in clinical response to different brands of enzymes. This has prompted the US Food and Drug Administration to require that enzyme supplements be subjected to New Drug Applications. AIM: To investigate the safety and efficacy of supplemental pancreatic enzyme therapy in cystic fibrosis subjects. METHODS: We compared two doses of one formulation of enteric-coated pancreatic enzymes: Ultrase MT12 (12,000 lipase units per capsule) and Ultrase MT20 (20,000 lipase units per capsule), to placebo in two separate safety and efficacy studies. RESULTS: Mean total fat, protein and carbohydrate intake did not differ significantly between the groups. A significant difference in both fat and protein absorption occurred with the enzyme therapy groups. The Ultrase MT12 and Ultrase MT20 groups experienced a mean fat and protein absorption 79.4% and 83.8%, and 87.3% and 88.6%, respectively. No adverse events related to study drug were reported. CONCLUSIONS: This study further supports the use of enzymes to treat pancreatic insufficiency in cystic fibrosis. Excellent fat and protein absorption was achieved with minimal adverse events and safe doses.

Adolescent↗
PubMed2003

Modulation of [3H] TBOB binding to the rodent GABAA receptor by simple disaccharides.

We have recently reported evidence that a simple beta-linked alkylated mannose reversibly increased the magnitude of GABA(A) receptor currents evoked in cultured rat pyramidal neurons whilst concomitantly reducing the incidence of spontaneous synaptic activity. In this present study, the effects of the simple beta-linked disaccharide, lactose was investigated using a [3H] TBOB (t-[3H] butylbicycloorthobenzoate) binding assay in adult rat forebrain and cerebellum membranes. Lactose elicited a significant potentiation of [3H] TBOB binding to well-washed forebrain and cerebellar membranes (mean E(max) values=367 and 287%; mean EC(50) values=1.5 and 30 microM, respectively, N=4). The alpha-linked disaccharides, maltose and sucrose also potentiated [3H] TBOB binding, but with 100-600-fold higher EC(50) values than lactose. The lactose-mediated potentiation of [3H] TBOB in the forebrain and cerebellum was completely abolished in the presence of 0.3 microM GABA. Over the concentration range in which significant potentiation of [3H] TBOB binding was detected, lactose elicited no significant effect upon [3H] flunitrazepam binding. This study demonstrated that lactose can modulate the GABA(A) receptor channel, allosterically coupled to the agonist site, but independent of the benzodiazepine site. Furthermore, lactose displayed differential effects upon forebrain and cerebellar GABA(A) receptors indicating that it may be a novel subtype selective agent.

Animals↗
PubMed2002

Active fluidization of polymer networks through molecular motors.

Entangled polymer solutions and melts exhibit elastic, solid-like resistance to quick deformations and a viscous, fluid-like response to slow deformations. This viscoelastic behaviour reflects the dynamics of individual polymer chains driven by brownian motion: since individual chains can only move in a snake-like fashion through the mesh of surrounding polymer molecules, their diffusive transport, described by reptation, is so slow that the relaxation of suddenly imposed stress is delayed. Entangled polymer solutions and melts therefore elastically resist deforming motions that occur faster than the stress relaxation time. Here we show that the protein myosin II permits active control over the viscoelastic behaviour of actin filament solutions. We find that when each actin filament in a polymerized actin solution interacts with at least one myosin minifilament, the stress relaxation time of the polymer solution is significantly shortened. We attribute this effect to myosin's action as a 'molecular motor', which allows it to interact with randomly oriented actin filaments and push them through the solution, thus enhancing longitudinal filament motion. By superseding reptation with sliding motion, the molecular motors thus overcome a fundamental principle of complex fluids: that only depolymerization makes an entangled, isotropic polymer solution fluid for quick deformations.

Actins↗
PubMed2002

Desire for information about drugs: relationships with patients' characteristics and adverse effects.

INTRODUCTION: Adverse effects of drugs are known to cause problems both in hospital and general practice settings, contributing to longer stays in a hospital, and increased costs of hospitalisation. By developing both a greater understanding of adverse drug reactions and effects and developing ways to reduce them will assist pharmacists in managing medicines more effectively. The aim of this study was to explore the relationships between patient characteristics, information requirements and perceptions about adverse drug effects to assist pharmacists in identifying patients most at risk of ADRs. METHODS: The study took place on medical wards at a London teaching hospital during an eight week period in Autumn 2000. Patients were recruited using convenience sampling during the recruitment period. Once eligible patients consented to take part, standardised interviews were conducted at their bedside. The interviews included the use of the previously validated scale which measures the extent of information desired (EID), patient characteristics including age, gender, socio-economic status etc and the presence of an adverse drug effect was assessed using the Naranjo algorithm. Patients were also asked semi-structured questions to explore past and present experiences of adverse drug effects. RESULTS: 82 patients were recruited, 80 were eligible for adverse effects of drugs assessment. Fifteen percent (12/80) of patients were assessed as having "definite" and "probable" adverse drug effects, based on the Naranjo algorithm. The previously validated EID scale was found to be both valid and reliable in this patient sample. There was an association between high scores on the EID scale and the presence of an adverse drug effect (chi-squared = 4.97, p = 0.02). CONCLUSION: The results show an association between the occurrence of an adverse drug effect on admission (identified by the Naranjo scale), the experience of an adverse drug effect in the past and a patient's desire for information. The EID-scale could be developed into a useful tool for assessing and addressing patients' drug information needs for pharmacists to use when assessing adverse drug effects in everyday practice.

Adult↗
PubMed2001

Antidepressant drugs and generic counselling for treatment of major depression in primary care: randomised trial with patient preference arms.

OBJECTIVES: To compare the efficacy of antidepressant drugs and generic counselling for treating mild to moderate depression in general practice. To determine whether the outcomes were similar for patients with randomly allocated treatment and those expressing a treatment preference. DESIGN: Randomised controlled trial, with patient preference arms. Follow up at 8 weeks and 12 months and abstraction of GP case notes. SETTING: 31 general practices in Trent region. PARTICIPANTS: Patients aged 18-70 who met research diagnostic criteria for major depression; 103 patients were randomised and 220 patients were recruited to the preference arms. MAIN OUTCOME MEASURES: Difference in mean Beck depression inventory score; time to remission; global outcome assessed by a psychiatrist using all data sources; and research diagnostic criteria. RESULTS: At 12 months there was no difference between the mean Beck scores in the randomised arms. Combining the randomised and patient preference groups, the difference in Beck scores was 0.4 (95% confidence interval -2.7 to 3.5). Patients choosing counselling did better than those randomised to it (mean difference in Beck score 4.6, 0.0 to 9.2). There was no difference in the psychiatrist's overall assessment of outcome between any of the groups. 221/265 (83%) of participants with a known outcome had a remission. Median time to remission was shorter in the group randomised to antidepressants than the other three groups (2 months v 3 months). 33/221 (15%) patients had a relapse. CONCLUSIONS: Generic counselling seems to be as effective as antidepressant treatment for mild to moderate depressive illness, although patients receiving antidepressants may recover more quickly. General practitioners should allow patients to have their preferred treatment.

Adult↗
PubMed2001

The attitudes of 'tomorrow's doctors' towards mental illness and psychiatry: changes during the final undergraduate year.

AIMS: To compare the efficacy of two teaching styles, didactic teaching and problem based learning, in producing enduring change in final-year medical students' attitudes towards psychiatry and mental illness. METHOD: A 1-year follow-up questionnaire survey of two groups of medical students taught psychiatry in their fourth-year training by two different methods. One-year follow-up scores were compared with pre-attachment and post-attachment scores in the fourth year. RESULTS: 70 (68%) students completed both questionnaires at follow-up. The follow-up scores were significantly lower compared with both the fourth-year pre-attachment and post-attachment scores, suggesting that the positive change in attitudes following psychiatric training in the fourth year significantly decayed during the final year. The two teaching methods did not differ in the magnitude of this reduction. CONCLUSIONS: The positive change that occurs in medical students' attitude towards psychiatry, psychiatrists and mental illness after their fourth-year psychiatric training is transient and decays over the final year.

Attitude↗
PubMed2001

Nutritional and other postoperative management of neonates with short bowel syndrome correlates with clinical outcomes.

OBJECTIVE: To determine correlates of clinical outcomes in patients with short bowel syndrome (SBS). METHODS: Retrospective medical record review of neonates treated between 1986 and 1998 who met our criteria for SBS: dependence on parenteral nutrition (PN) for at least 90 days after surgical therapy for congenital or acquired intestinal diseases. RESULTS: Thirty subjects with complete data were identified; 13 (43%) had necrotizing enterocolitis, and 17 (57%)had intestinal malformations. Mean (SD) residual small bowel length was 83 (67) cm. Enteral feeding with breastmilk (r = -0.821) or an amino acid-based formula (r = -0.793) was associated with a shorter duration of PN, as were longer residual small bowel length (r = -0.475) and percentage of calories received enterally at 6 weeks after surgery(r = -0.527). Shorter time without diverting ileostomy or colostomy (r = 0.400), enteral feeding with a protein hydrolysate formula (r = -0.476), and percentage of calories received enterally at 6 weeks after surgery (r = -0.504) were associated with a lower peak direct bilirubin concentration. Presence of an intact ileocecal valve and frequency of catheter-related infections were not significantly correlated with duration of PN. In multivariate analysis, only residual small bowel length was a significant independent predictor of duration of PN, and only less time with a diverting ostomy was an independent predictor of peak direct bilirubin concentration. CONCLUSIONS: Although residual small bowel length remains an important predictor of duration of PN use in infants with SBS, other factors, such as use of breast milk or amino acid-based formula, may also play a role in intestinal adaptation. In addition, prompt restoration of intestinal continuity is associated with lowered risk of cholestatic liver disease. Early enteral feeding after surgery is associated both with reduced duration of PN and less cholestasis.

Adaptation, Physiological↗
PubMed2001

Cysteine metabolism and whole blood glutathione synthesis in septic pediatric patients.

OBJECTIVE: To investigate whole body in vivo cysteine kinetics and its relationship to whole blood glutathione (GSH) synthesis rates in septic, critically ill pediatric patients and controls. DESIGN: Prospective cohort study. SETTING: Multidisciplinary intensive care unit and pediatric inpatient units at a children's hospital. PATIENTS: Ten septic pediatric patients and ten controls (children admitted to the hospital for elective surgery). INTERVENTIONS: Septic patients (age, 31 months to 17 yrs) and controls (age, 24 months to 21 yrs) received a 6-hr primed, constant, intravenous tracer infusion of l-[1-13C]cysteine. Blood samples were obtained to determine isotopic enrichment of plasma cysteine and whole blood [1-13C]cysteinyl-glutathione by gas-chromatography mass spectrometric techniques. The plasma flux and oxidation rate of cysteine and the fractional and absolute synthesis rates of GSH were determined. Septic patients received variable protein and energy intake, as per routine clinical management, and controls were studied in the early postabsorptive state. MEASUREMENTS AND MAIN RESULTS: Plasma cysteine fluxes were increased in the septic patients when compared with the controls (68.2 +/- 17.5 [sd] vs. 48.7 +/- 8.8 micromol x kg(-1) x hr(-1); p <.01), and the fraction of plasma cysteine flux associated with oxidative disposal was similar among the groups. The absolute rates of GSH synthesis in whole blood were decreased (p <.01) in the septic patients (368 +/- 156 vs. 909 +/- 272 micromol x L(-1) x day(-1)). The concentration of whole blood GSH also was decreased in the septic group (665.4 +/- 194 vs. 1059 +/- 334 microM; p <.01) CONCLUSIONS: Whole blood glutathione synthesis rates are decreased, by about 60%, in critically ill septic children receiving limited nutritional support. Plasma cysteine fluxes and concentration of cysteine were increased in the septic patients, suggesting a hypermetabolic state with increased protein breakdown. The mechanisms whereby GSH synthesis rates are decreased in these patients are probably multifactorial, presumably involving an inflammatory response in the presence of limited nutritional support. The role of nutritional modulation and the use of cysteine prodrugs in maintaining GSH concentration and synthesis remain to be established.

Adolescent↗
PubMed2001

Micronutrients and child health: studies in international nutrition and HIV infection.

Increasing data link micronutrient deficiencies to excess childhood morbidity and mortality, and similar relationships have been noted in the study of nutrition and HIV infection. We review epidemiologic studies that have examined the relationship between micronutrient deficiencies and health outcomes in childhood and HIV infection, as well as clinical trials of micronutrient supplementation. Vitamin A supplementation among communities at risk of deficiency effectively reduces mortality and morbidity in children younger than age 5, and vitamin A may be especially effective in HIV-infected children. Vertical transmission of HIV has not to date been affected by maternal micronutrient supplementation. In children with poor dietary zinc intake and/or bioavailability, zinc supplementation reduces the incidence and severity of diarrheal diseases, as well as the occurrence of pneumonia. Vitamin A therapy has not been associated with improved growth, whereas some trials have shown that zinc supplementation is associated with greater increments in height. Further trials of micronutrient supplementation are warranted.

Child↗
PubMed2001

Effective progenitor cell mobilization in lymphoproliferative disorders using ifosfamide, epirubicin and etoposide (IEV).

The combination of ifosfamide, epirubicin and etoposide (IEV) is an effective salvage regimen for lymphoproliferative disease. We report our experience with this combination in mobilization of peripheral blood stem cells (PBSC) in patients with relapsed or refractory/high-risk lymphoma. The median time to leukapheresis was 14 days, with 85% of patients commencing PBSC collection in the range of 13-15 days. Mobilization was successful in 26 of 28 patients (93%), who achieved the minimum transplant dose of 2 x 10(6)/kg CD34+ cells in a median of 2 leukaphereses. Overall, the median CD34+ cell yield was 6.94 x 10(6)/kg (range 0.73-27.4). In 15 of 27 patients (54%), the yield was sufficient (> 6 x 10(6)/kg) to permit CD34+ cell selection and/or a second autograft. IEV was given as an inpatient in all cases. Patients were scheduled for discharge after chemotherapy. This was achieved in 71%, with readmission 1 week later for harvest. Therapy was complicated by neutropenic fever in 13 patients and mild nausea. In autografts carried out using IEV-mobilized PBSC (n = 20), the median time to neutrophils > 0.5 x 10(9)/L was 10 days (range 7-13 days), and to platelets > 20 x 10(9)/L was 13 days (range 11-18 days). There was no mobilization- or transplant-related mortality. We conclude that IEV is a safe, predictable and highly effective mobilization regimen in patients with lymphoma.

Adolescent↗