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Biomedical subjects

G Cleghorn

Publications and source records attributed to G Cleghorn.

At least 19 recordsLinked to original sources

Malnutrition among gynaecological cancer patients.

OBJECTIVE: To assess the nutritional status of patients with gynaecological cancer. DESIGN: A prospective study assessing the nutritional status of gynaecological patients with suspected or proven gynaecological cancer. SETTING: Queensland Centre for Gynaecological Cancer, Brisbane, Australia; a tertiary referral centre for gynaecological cancer. SUBJECTS: One hundred forty-five patients with suspected or proven gynaecological cancer aged 20-91 years. INTERVENTION: Scored patient-generated subjective global assessment (PG-SGA) and serum albumin before treatment. RESULTS: One hundred and sixteen (80%) patients were categorized as PG-SGA class A, 29 (20%) patients were PG-SGA B and none of the patients were PG-SGA C. Ovarian cancer patients had significantly lower serum albumin levels (P=0.003) and higher PG-SGA scores (P<0.001) than patients with other types of cancer and benign conditions. Sixty-seven per cent of patients with ovarian cancer were classified as PG-SGA B. After adjusting for patient's age, body mass index and albumin level, ovarian cancer patients were 19 times more likely to be categorized as PG-SGA class B compared to patients with benign conditions (95% confidence interval: 3.03-129.8; P=0.002). CONCLUSION: Malnutrition in gynaecological cancer patients is a significant problem, especially among those patients diagnosed with ovarian cancer.

Adult↗

Centile reference charts for total energy expenditure in infants from 1 to 12 months.

BACKGROUND: A knowledge of energy expenditure in infancy is required for the estimation of recommended daily amounts of food energy, for designing artificial infant feeds, and as a reference standard for studies of energy metabolism in disease states. OBJECTIVES: The objectives of this study were to construct centile reference charts for total energy expenditure (TEE) in infants across the first year of life. METHODS: Repeated measures of TEE using the doubly labeled water technique were made in 162 infants at 1.5, 3, 6, 9 and 12 months. In total, 322 TEE measurements were obtained. The LMS method with maximum penalized likelihood was used to construct the centile reference charts. Centiles were constructed for TEE expressed as MJ/day and also expressed relative to body weight (BW) and fat-free mass (FFM). RESULTS: TEE increased with age and was 1.40,1.86, 2.64, 3.07 and 3.65 MJ/day at 1.5, 3, 6, 9 and 12 months, respectively. The standard deviations were 0.43, 0.47, 0.52,0.66 and 0.88, respectively. TEE in MJ/kg increased from 0.29 to 0.36 and in MJ/day/kg FFM from 0.36 to 0.48. CONCLUSIONS: We have presented centile reference charts for TEE expressed as MJ/day and expressed relative to BW and FFM in infants across the first year of life. There was a wide variation or biological scatter in TEE values seen at all ages. We suggest that these centile charts may be used to assess and possibly quantify abnormal energy metabolism in disease states in infants.

Administration, Oral↗

A highly efficient and consistent method for harvesting large volumes of high-titre lentiviral vectors.

Lentiviral vectors pseudotyped with vesicular stomatitis virus glycoprotein (VSV-G) are emerging as the vectors of choice for in vitro and in vivo gene therapy studies. However, the current method for harvesting lentivectors relies upon ultracentrifugation at 50,000 g for 2 h. At this ultra-high speed, rotors currently in use generally have small volume capacity. Therefore, preparations of large volumes of high-titre vectors are time-consuming and laborious to perform. In the present study, viral vector supernatant harvests from vector-producing cells (VPCs) were pre-treated with various amounts of poly-L-lysine (PLL) and concentrated by low speed centrifugation. Optimal conditions were established when 0.005% of PLL (w/v) was added to vector supernatant harvests, followed by incubation for 30 min and centrifugation at 10,000 g for 2 h at 4 degrees C. Direct comparison with ultracentrifugation demonstrated that the new method consistently produced larger volumes (6 ml) of high-titre viral vector at 1 x 10(8) transduction unit (TU)/ml (from about 3,000 ml of supernatant) in one round of concentration. Electron microscopic analysis showed that PLL/viral vector formed complexes, which probably facilitated easy precipitation at low-speed concentration (10,000 g), a speed which does not usually precipitate viral particles efficiently. Transfection of several cell lines in vitro and transduction in vivo in the liver with the lentivector/PLL complexes demonstrated efficient gene transfer without any significant signs of toxicity. These results suggest that the new method provides a convenient means for harvesting large volumes of high-titre lentivectors, facilitate gene therapy experiments in large animal or human gene therapy trials, in which large amounts of lentiviral vectors are a prerequisite.

Animals↗

Assistance arrangements and use of services among persons with multiple sclerosis and their caregivers.

A large population-based survey of persons with multiple sclerosis (MS) and their caregivers was conducted in Ontario using self-completed mailed questionnaires. The objectives included describing assistance arrangements, needs, and use of and satisfaction with services, and comparing perceptions of persons with MS and their caregivers. Response rates were 83% and 72% for those with MS and caregivers, respectively. Based on 697 respondents with MS whose mean age is 48 years, 70% are female, and 75% are married. While 24% experience no mobility restrictions, the majority require some type of aid or a wheelchair for getting around. Among 345 caregivers, who have been providing care for 9 years on average, the majority are spouses. Caregivers report providing more frequent care than do persons with MS report receiving it, particularly for the following activities of daily living: eating, meal preparation, and help with personal finances. Caregivers also report assistance of longer duration per day than do care recipients with MS. Frequency and duration of assistance are positively associated with increased MS symptom severity and reduced mobility. Generally there is no rural-urban disparity in service provision, utilization or satisfaction, and although there is a wide range of service utilization, satisfaction is consistently high. Respite care is rarely used by caregivers. Use of several services is positively associated with increased severity of MS symptoms and reduced mobility. Assistance arrangements and use of services, each from the point of view of persons with MS and their caregivers, must be taken into account in efforts to prolong home care and to postpone early institutionalization of persons with MS.

Activities of Daily Living↗

Acceptability of a rice-based oral rehydration solution in Port Moresby General Hospital's Children's Outpatient Department.

The guardians of children brought to the Port Moresby General Hospital's Children's Outpatient Department with a chief complaint of diarrhoeal disease were questioned regarding their preference of glucose-based vs rice-based oral rehydration solution (ORS) in order to determine the acceptability of a rice-based ORS. Of the 93 guardians interviewed, greater than 60% preferred the glucose-based solution in its mixability, appearance and taste, and 65% initially reported that their children preferred the taste of the glucose solution. However, after a 30-minute trial, only 58% of children still preferred the glucose solution. In a country where diarrhoeal disease is a leading cause of child death and guardians are the primary health care providers, the acceptability of an ORS is critical to the morbidity and mortality of Papua New Guinea's children.

Adult↗

A 3-hour quantitative comparison of glucose-based versus rice-based oral rehydration solution intake by children with diarrhoea in Port Moresby General Hospital.

Measurements were made of the intake of a WHO/UNICEF glucose-based and a rice cereal-based oral rehydration solution (ORS) by children with diarrhoea. Twenty children who presented to the Children's Outpatient Department at Port Moresby General Hospital with acute diarrhoea and mild dehydration were randomly assigned to an ORS and measurements were taken over the following 3 hours. For data analysis, the patients were paired by weight. Testing the means of the paired samples by t test showed that there was no significant difference between the amount of rice ORS and the amount of glucose ORS taken over 3 hours.

Body Weight↗

The treatment of recurrent abdominal pain in children: a controlled comparison of cognitive-behavioral family intervention and standard pediatric care.

This study describes the results of a controlled clinical trial involving 44 7- to 14-year-old children with recurrent abdominal pain who were randomly allocated to either cognitive-behavioral family intervention (CBFI) or standard pediatric care (SPC). Both treatment conditions resulted in significant improvements on measures of pain intensity and pain behavior. However, the children receiving CBFI had a higher rate of complete elimination of pain, lower levels of relapse at 6- and 12-month follow-up, and lower levels of interference with their activities as a result of pain and parents reported a higher level of satisfaction with the treatment than children receiving SPC. After controlling for pretreatment levels of pain, children's active self-coping and mothers' caregiving strategies were significant independent predictors of pain behavior at posttreatment.

Abdominal Pain↗

Serum immunoglobulin G directed against porcine trypsin in the serum of cystic fibrosis children receiving porcine pancreatic enzyme supplements.

Cystic fibrosis (CF) patients require pancreatic enzyme replacement therapy to correct pancreatic insufficiency. These enzymes are derived from porcine pancreas and are known to be antigenic. To determine the possible clinical consequences, a specific ELISA was developed to detect IgG antibody directed against porcine trypsin (PTAb) in the sera of CF patients. The assay was used to evaluate the occurrence of PTAb in a cross sectional study of 103 CF patients in relation to the introduction of porcine enzyme therapy, clinical status and genotype. Antibodies against porcine trypsin were detected in the sera of 63% of patients unrelated to the age of commencement or the duration of enzyme therapy. No differences were observed in the clinical status of CF patients who had developed PTAb (n = 65) and those who had no detectable PTAb (n = 38) as determined from: the current prescribed dose of porcine pancreatic enzyme capsules; Z scores for height and weight; and respiratory function tests. It is suggested that the PTAb commonly found in the sera of CF patients are of doubtful clinical significance but the prospect of PTAb contributing to immune complex disease should be examined further.

Adolescent↗

Osmolality electrolyte and carbohydrate type and oral rehydration solutions: a controlled study to compare the efficacy of two commercially available solutions (osmolalities 240 mmol/L and 340 mmol/L).

An open-label, inpatient study was undertaken to compare the efficacy of two oral rehydration solutions (ORS) given randomly to children aged 1-10 years who had acute gastroenteritis with mild or moderate dehydration (n = 45). One solution contained 60 mmol/l sodium and 1.8% glucose, total osmolality 240 mosm/l (Gastrolyte, Rhone-poulenc, Rorer) and the other contained 26 mmol/l sodium, 2.7% glucose and 3.6% sucrose, total osmolality 340 mOsm/l (Glucolyte, Gilseal). Analysis of data indicated that Gastrolyte therapy resulted in significantly fewer episodes and volume of vomiting over all time periods in comparison to Glucolyte and significantly less stool volume during the first 8 h and in the 0-24 h period. The differences between treatments in degree of dehydration at each follow-up period, duration of diarrhoea, and duration of hospital stay were not significant. No adverse drug reactions occurred. Six patients received intravenous rehydration treatment and were considered treatment failures. We conclude that oral rehydration therapy is safe and efficacious in the management of dehydration in acute diarrhoea and that the lower osmolar rehydration solution has clinically marginal advantages.

Acute Disease↗

The bentiromide test using plasma p-aminobenzoic acid for diagnosing pancreatic insufficiency in young children. The effect of two different doses and a liquid meal.

The bentiromide test was evaluated using plasma p-aminobenzoic acid as an indirect test of pancreatic insufficiency in young children between 2 months and 4 years of age. To determine the optimal test method, the following were examined: (a) the best dose of bentiromide (15 mg/kg or 30 mg/kg); (b) the optimal sampling time for plasma p-aminobenzoic acid; and (c) the effect of coadministration of a liquid meal. Sixty-nine children 91.6 +/- 1.0 years) were studied, including 34 controls with normal fat absorption and 35 patients (34 with cystic fibrosis) with fat maldigestion due to pancreatic insufficiency. Control and pancreatic insufficient subjects were studied in three age-matched groups: (a) low-dose bentiromide (15 mg/kg) with clear fluids; (b) high-dose bentiromide (30 mg/kg) with clear fluids; and (c) high-dose bentiromide with a liquid meal. Plasma p-aminobenzoic acid was determined at 0, 30, 60, and 90 minutes then hourly for 6 hours. The dose effect of bentiromide with clear liquids was evaluated. High-dose bentiromide best discriminated control and pancreatic insufficient subjects, due to a higher peak plasma p-aminobenzoic acid level in controls, but poor sensitivity and specificity remained. High-dose bentiromide with a liquid meal produced a delayed increase in plasma p-aminobenzoic acid in the control subjects probably caused by retarded gastric emptying. However, in the pancreatic insufficient subjects, use of a liquid meal resulted in significantly lower plasma p-aminobenzoic acid levels at all time points; plasma p-aminobenzoic acid at 2 and 3 hours completely discriminated between control and pancreatic insufficient patients. Evaluation of the data by area under the time-concentration curve failed to improve test results. In conclusion, the bentiromide test is a simple, clinically useful means of detecting pancreatic insufficiency in young children, but a higher dose administered with a liquid meal is recommended.

4-Aminobenzoic Acid↗

Evaluation of growth and changes in body composition following neonatal diagnosis of cystic fibrosis.

Early deficits in nutritional status that might require specific treatment and early response to nutritional therapy were studied longitudinally in 25 infants with cystic fibrosis (CF) diagnosed by neonatal screening, using anthropometric and research body composition methodology, and evaluation of pancreatic function. At the time of confirmed diagnosis (mean 5.4 weeks), body mass, length, total body fat (TBF), and total body potassium (TBK) were all significantly reduced. Following diagnosis and commencement of therapy there was a normalization of weight, length, and TBK by 6-12 months of age, indicating catch-up growth. But in some individuals the response was incomplete, and as a group, mean total body fat remained significantly lower than normal at 1 year of age. Seven of 25 (28%) were pancreatic sufficient at diagnosis, and all but one had evidence of declining pancreatic function requiring the institution of pancreatic enzyme therapy during the next 1-9 months. The median age of commencement of enzyme therapy was 10 weeks (range 5 weeks to 11 months). These longitudinal assessments emphasize the dynamic changes occurring in absorptive function, body composition, and nutritional status following neonatal diagnosis of cystic fibrosis and may reflect previously described abnormalities of energy metabolism in this age group. Abnormal body composition is evident in most CF infants following diagnosis by neonatal screening but pancreatic damage may still be evolving. We suggest that early active nutritional therapy and surveillance for changes in pancreatic function are warranted in CF infants diagnosed by neonatal screening.

Body Composition↗

Serum immunoglobulin G directed against porcine trypsin in pancreatic insufficient cystic fibrosis patients receiving pancreatic enzyme supplements.

Cystic fibrosis (CF) patients frequently malabsorb nutrients because of pancreatic failure. Standard therapy entails oral administration of porcine pancreatic enzymes, with meals. Porcine enzymes contain in excess of 25 potentially antigenic proteins. To evaluate antigenicity of one of these (porcine trypsin), we developed ELISA techniques capable of measuring total immunoglobulin G (IgG) and IgG directed against porcine trypsin in patient sera. Cross-sectional evaluation of sera from 12 controls and 41 CF patients showed that IgG directed against porcine trypsin was detectable in 12/17 CF patients receiving porcine enzymes (50.6 +/- 56.0 ng/ml; range 0-154.0 ng/ml), while none was detected in controls or the 26 CF subjects not receiving enzymes. In the 17 CF patients receiving enzymes, porcine trypsin binding IgG contributed 0.85 +/- 0.83% of the total IgG pool. Levels of porcine trypsin binding did not correlate with total IgG. Longitudinal evaluation was then performed in 26 CF patients, before and after commencement of enzyme therapy. Prior to commencing therapy, porcine trypsin binding IgG was undetectable in sera from 24/26 patients. Within 4.2 years of commencing therapy, 25/26 patients (96%) developed porcine trypsin binding IgG. Thus, serum IgG responses to porcine trypsin appear to be common in CF patients receiving porcine enzymes and contribute considerably to total IgG levels. Other individual enzymes in porcine extracts are likely to elicit similar antigenic response.

Administration, Oral↗

Cyclosporin-responsive enteropathy and protracted diarrhea.

We describe a child born to unrelated parents who developed severe protracted secretory type diarrhea associated with subtotal villus atrophy and intestinal inflammation at the age of 19 months. No infectious, metabolic, or anatomical basis for this condition was identified and the child required total parenteral nutrition for a period of 18 months despite trials of special enteral formulas, steroids, and anti-inflammatory agents. This refractory "enteropathy" responded dramatically to the introduction of cyclosporin, with cessation of the secretory diarrhea, recovery from the enteropathy, and cessation of parenteral nutrition. The symptoms relapsed when cyclosporin was briefly discontinued and improved following reintroduction of this drug. This experience suggests a role for immune factors in the pathogenesis of the enteropathy in this case and that a trial of cyclosporin is worthy of consideration in similar cases.

Cyclosporins↗

Short-term nutritional supplementation during management of pulmonary exacerbations in cystic fibrosis: a controlled study, including effects of protein turnover.

Effects of nutritional supplements on minimizing weight loss and abnormalities of protein turnover during pulmonary exacerbations in cystic fibrosis (CF) were studied by controlled trial. Patients received pulmonary therapy and either standard diet (n = 10) or adjunctive enteral supplements (n = 12). Initial protein turnover, measured by [15N]glycine kinetics, showed alterations of protein synthesis (P Syn) and catabolism (P Cat), which correlated with the degree of underweight, and negligible net protein deposition (P Dep). With treatment both groups had significant increases in mean body weight and forced expiratory volume in 1 s, expressed as percent predicted value for height (FEV1) by 3 wk, but a significant correlation between initial underweight and subsequent weight gain was observed only in supplemented patients. Mean P Syn and P Dep increased significantly (p less than 0.001) only in the supplemented group. Pulmonary exacerbations in CF have important adverse effects on body-protein metabolism, similar to changes in protein-energy malnutrition and infection. These effects are reversed by short-term nutritional support. Strategic nutritional intervention should thus be considered in management, especially in malnourished patients.

Adolescent↗