G. J. Cleghorn

Survival, growth and quality of life in children after orthotopic liver transplantation : a 5 year experience

The aims of this study were to investigate outcome and to evaluate areas of potential ongoing concern after orthotopic liver transplantation (OLT) in children. Actuarial survival in relation to age and degree of undernutrition at the time of OLT was evaluated in 53 children (age 0.58‐14.2 years) undergoing OLT for endstage liver disease. Follow‐up studies of growth and quality of life were undertaken in those with a minimum follow‐up period of 12 months (n= 26). The overall 3 year actuarial survival was 70%. Survival rates did not differ between age groups (actuarial 2 year survival for ages <1,1‐5 and >5 years were 70, 70 and 69% respectively) but did differ according to nutritional status at OLT (actuarial 2 year survival for children with Z scores for weight <−1 was 57%, >−1 was 95%; P=0.004). Significant catch‐up weight gain was observed by 18 months post‐transplant, while height improved less rapidly. Quality of life (assessed by Vineland Adaptive Behaviour Scales incorporating socialization, daily living skills, communication and motor skills) was good (mean composite score 91±19). All school‐aged children except one were attending normal school. Two children had mild to moderate intellectual handicap related to post‐operative intracerebral complications. Satisfactory long‐term survival can be achieved after OLT in children regardless of age but the importance of pre‐operative nutrition is emphasized. Survivors have an excellent chance of a good quality of life and of satisfactory catch‐up weight gain and growth.

Dichotomy of food and inhalant allergen sensitization in eosinophilic esophagitis.

Background:  Eosinophilic esophagitis (EE) is an emerging condition where patients commonly present with symptoms of gastroesophageal reflux disease and fail to respond adequately to anti‐reflux therapy. Food allergy is currently recognized as the main immunological cause of EE; recent evidence suggests an etiological role for inhalant allergens. The presence of EE appears to be associated with other atopic illnesses.

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 patients 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.

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.

Nutritional rehabilitation in cystic fibrosis : a 5 year follow-up study

Summary Previously, we reported catch-up weight gain, growth, and improved lung function in a group of malnourished cystic fibrosis (CF) children receiving aggressive nutritional supplementation for 1 year compared with a forced expiratory volume in 1 s (FEV1)-, height-, and sex-matched comparison group receiving standard therapy. To evaluate long-term effects, the clinical progress of both groups has been studied over a 5 year period. The supplemented group (n = 10) received supplements for a median of 1.35 years to achieve nutritional rehabilitation. Compared with the nonsupplemented group (n = 14), the previously supplemented group had lower mortality (2 vs. 4, N.S.) and significantly greater weight and height z scores at 4 and 5 years. The progression of pulmonary function abnormalities as measured by FEV1 and forced vital capacity (FVC) slopes was greater at 3 years in the nonsupplemented group (FEV1, p < 0.05) but no significant differences in rates of deterioration of pulmonary function were seen after 5 years in the two groups of survivors. We conclude that intensive nutritional support for 1 year has both short- and long-term effects on nutrition and growth, still evident some years after the cessation of this therapeutic modality. Supplementation for periods of longer than 1 year may produce greater gains and possibly prolong the improvement in pulmonary function observed in the earlier study.

Malnutrition in children with chronic liver disease accepted for liver transplantation: Clinical profile and effect on outcome

Abstract  The nutritional profiles of 37 children (aged 0.5–14.0 years) with chronic liver disease at the time of acceptance for orthotopic liver transplantation (OLTP) have been evaluated using clinical, biochemical and body composition methods. Nutritional progress while waiting for a donor has been related to outcome, whether transplanted or not. At the time of acceptance, most children were underweight (mean standard deviation (s.d.) weight = 1.4±0.2) and stunted (mean s.d. height = ‐ 2.2±0.4), had low serum albumin (27/35) and had reduced body fat and depleted body cell mass (measured by total body potassium ‐ mean % expected for age = 58±5%, n= 15). Mean ad libitum nutrient intake was 63±5% of recommended daily intake (RDI). Those who died while waiting (n= 8) had significantly lower mean initial s.d. weight compared with those transplanted. The overall actuarial 1 year survival of those who were transplanted (mean waiting time = 75 days) was 81% but those who were initially well nourished (s.d. weight > ‐ 1.0) had an actuarial 1 year survival of 100%. There were no significant differences in actuarial survival in relationship to age, type of transplant (whole liver or segmental), liver biochemistry or the presence or absence of ascites. Of the total group accepted for OLTP, whether transplanted or not, the overall 1 year survival for those who were relatively well nourished was 88% and for those undernourished (initial s.d. weight > ‐ 1.0) was 38% (P<0.003). Declining nutritional status during the waiting period also adversely affected outcome. We conclude that malnutrition and/or declining nutritional status is a major factor adversely affecting survival in children awaiting OLTP. In transplant units where waiting time is greater than 40 days, earlier referral, prioritization of cases and the use of adult donor livers may reduce this risk and efforts to maintain or improve nutritional status deserve further study.

Validity of BMI as a measure of obesity in Australian white Caucasian and Australian Sri Lankan children

Background: Body mass index (BMI) is used to diagnose obesity. However, its ability to predict the percentage fat mass (%FM) reliably is doubtful. Therefore validity of BMI as a diagnostic tool of obesity is questioned. Aim: This study is focused on determining the ability of BMI-based cut-off values in diagnosing obesity among Australian children of white Caucasian and Sri Lankan origin. Subjects and methods: Height and weight was measured and BMI (W/H2) calculated. Total body water was determined by deuterium dilution technique and fat free mass and hence fat mass derived using age- and gender-specific constants. A %FM of 30% for girls and 20% for boys was considered as the criterion cut-off level for obesity. BMI-based obesity cut-offs described by the International Obesity Task Force (IOTF), CDC/NCHS centile charts and BMI-Z were validated against the criterion method. Results: There were 96 white Caucasian and 42 Sri Lankan children. Of the white Caucasians, 19 (36%) girls and 29 (66%) boys, and of the Sri Lankans 7 (46%) girls and 16 (63%) boys, were obese based on %FM. The FM and BMI were closely associated in both Caucasians (r = 0.81, P<0.001) and Sri Lankans (r = 0.92, P<0.001). Percentage FM and BMI also had a lower but significant association. Obesity cut-off values recommended by IOTF failed to detect a single case of obesity in either group. However, NCHS and BMI-Z cut-offs detected cases of obesity with low sensitivity. Conclusions: BMI is a poor indicator of percentage fat and the commonly used cut-off values were not sensitive enough to detect cases of childhood obesity in this study. In order to improve the diagnosis of obesity, either BMI cut-off values should be revised to increase the sensitivity or the possibility of using other indirect methods of estimating the %FM should be explored.

Colonoscopy preparation in children: safety, efficacy, and tolerance of high- versus low-volume cleansing methods.

BACKGROUND The use of large-volume electrolyte balanced solutions as preparation for colonoscopy often results in poor patient compliance and acceptance. The tolerance, safety, and efficacy of high-versus low-volume colon-cleansing methods as preparation for colonoscopy in children were compared by randomized operator-blinded trial. METHODS Twenty-nine children ages 3.6-14.6 years had either high-volume nasogastric balanced polyethylene glycol electrolyte lavage (20 ml/kg/ h) until the effluent was clear (n = 15), or two oral doses of sodium phosphate solution (22.5-45 ml) separated by oral fluid intake (n = 14). RESULTS Both preparations were equally effective. The low-volume preparation was better tolerated and caused less discomfort that the high-volume preparation, judging by serial nurse observations. The incidence of abdominal symptoms, diarrhea, sleep disturbance, and vomiting was not significantly different between the two groups. Both groups had a small reduction in mean hematocrit and serum calcium levels. The sodium phosphate preparation caused increases in mean serum sodium concentrations from 140 to 145 mmol/L and serum phosphate concentrations from 1.41 to 2.53 mmol/L. Ten hours after the commencement of the preanesthetic fast, these concentrations had returned to normal. CONCLUSIONS There are advantages in terms of tolerance, discomfort, and case of administration with acceptable colonic cleansing with the use of the less-invasive oral sodium phosphate low-volume colon-cleansing preparation in children. Safe use requires ensuring an adequate oral fluid intake during the preparation time and avoidance of use in patients with renal insufficiency.

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 50000 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 10000 g for 2 h at 4°C. Direct comparison with ultracentrifugation demonstrated that the new method consistently produced larger volumes (6 ml) of high-titre viral vector at 1 × 108 transduction unit (TU)/ml (from about 3000 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 (10000 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.

Age-Related Alterations of Immunoreactive Pancreatic Cationic Trypsinogen in Sera from Cystic Fibrosis Patients with and without Pancreatic Insufficiency

ABSTRACT: Serum immunoreactive cationic trypsinogen levels were determined in 99 control subjects and 381 cystic fibrosis (CF) patients. To evaluate the status of the exocrine pancreas all CF patients had previously undergone fecal fat balance studies and/or pancreatic stimulation tests. Three hundred fourteen CF patients had fat malabsorption and/or had inadequate pancreatic enzyme secretion (pancreatic insufficiency) requiring oral pancreatic enzyme supplements with meals. Sixty-seven CF patients did not have fat malabsorption and/or had adequate enzyme secretion (pancreatic sufficiency) and were not receiving pancreatic enzyme supplements with meals. Mean serum trypsinogen in 99 control subjects was 31.4 ± 14.8 µg/liter (± 2 SD) and levels did not vary with age or sex. In CF infants (< 2 yr) with pancreatic insufficiency, mean serum trypsinogen was significantly above the non-CF values (p<0.001). Ninety-one percent of the CF infants had elevated levels. Serum trypsinogen values in the pancreatic insufficient group declined steeply up to 5 years, reaching subnormal values by age 6. An equation was developed which described these age-related changes very accurately. Only six CF patients with pancreatic insufficiency had serum trypsinogen levels above the 95% confidence limits of this equation. In contrast, there was no age related decline in serum trypsinogen among the CF group with pancreatic sufficiency. Under 7 yr, serum trypsinogen failed to distinguish the two groups. In those over 7 yr of age, however, serum trypsinogen was significantly higher than the CF group with pancreatic insufficiency (p<0.001), and 93% had values within or above the control range. In conclusion, serum trypsinogen appears to be a useful screening test for CF in infancy. Between 2 and 7 yr of age this test is of little diagnostic value. After 7 yr of age, serum trypsinogen can reliably distinguish between CF patients with and without pancreatic insufficiency.