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Biomedical subjects

R W Shepherd

Publications and source records attributed to R W Shepherd.

At least 37 records · Page 2Linked to original sources
PubMed1998

Contribution of hepatic parenchymal and nonparenchymal cells to hepatic fibrogenesis in biliary atresia.

Extrahepatic biliary atresia is a severe neonatal liver disease resulting from a sclerosing cholangiopathy of unknown etiology. Although biliary obstruction may be surgically corrected by a "Kasai" hepatoportoenterostomy, most patients still develop progressive hepatic fibrosis, although the source of increased collagen deposition is unclear. This study examined the role of hepatic stellate cells (HSCs) and assessed the source of transforming growth factor-beta (TGF-beta) production in hepatic fibrogenesis in patients with biliary atresia. Liver biopsies from 18 biliary atresia patients (including 5 pre- and post-Kasai) were subjected to immunohistochemistry for alpha-smooth muscle actin and in situ hybridization for either procollagen alpha1 (I) mRNA or TGF-beta1 mRNA. Sections were also subjected to immunohistochemistry for active TGF-beta1 protein. The role of Kupffer cells in TGF-beta1 production was assessed by immunohistochemistry for CD68. Procollagen alpha1 (I) mRNA was colocalized to alpha-smooth muscle actin-positive HSCs within the region of increased collagen protein deposition in fibrotic septa and surrounding hyperplastic bile ducts. The number of activated HSCs was decreased in only one post-Kasai biopsy. TGF-beta1 mRNA expression was demonstrated in bile duct epithelial cells and activated HSCs and in hepatocytes in close proximity to fibrotic septa. Active TGF-beta1 protein was demonstrated in bile duct epithelial cells and activated HSCs. This study provides evidence that activated HSCs are responsible for increased collagen production in patients with biliary atresia and therefore play a definitive role in the fibrogenic process. We have also shown that bile duct epithelial cells, HSCs, and hepatocytes are all involved in the production of the profibrogenic cytokine, TGF-beta1.

Actins↗
PubMed1998

Malnutrition, gastroenteritis and trypsinogen concentration in hospitalised Aboriginal children.

OBJECTIVE: To explore relationships between malnutrition and pancreatic damage in hospitalised aboriginal children. METHODS: Immunoreactive trypsinogen (IRT) concentrations were measured in two populations of hospitalised aboriginal children in Australia: 472 children aged 0-3 years, in Alice Springs (Northern Territory); and 187 children aged 0-16 years in Mount Isa (Queensland). Correlation of whole blood IRT with height and weight z-scores, four-site skinfold thickness and upper arm circumference was sought. RESULTS: In Mount Isa, the geometric mean IRT concentration rose with decreasing weight z-score. The IRT concentration was otherwise unrelated to nutritional indices. Sixty percent of the 39 Mount Isa patients with gastroenteritis and 24.5% of the 358 Alice Springs patients with gastroenteritis had an IRT concentration in the upper quartile for their population, compared with 16% for patients with other diagnoses in both populations. CONCLUSIONS: A high IRT concentration in patients with low weight z-scores is a confounding effect of gastroenteritis, and may result from subclinical pancreatic disease in gastroenteritis.

Adolescent↗
PubMed1998

The sleep patterns of infants and young children with gastro-oesophageal reflux.

OBJECTIVE: Sleep disturbance in gastro-oesophageal reflux disease (GORD) in infants and young children has not been systematically studied nor has this manifestation been compared with population norms. METHODS: Sleep patterns of 102 infants and children aged 1 to 36 months with and without GORD, defined by pH monitoring, were analysed using the same questionnaire as in recent studies of normal sleep behaviour in this age range. Main outcome measures included time taken to settle at night, the number of night time wakenings requiring parental intervention, day time sleep patterns and parents problems with their childs' sleep behaviour. RESULTS: Compared with the population norms (n=3102), those with GORD (n=76) had greater prevalence of night time waking >3/night (50% vs 13% aged 3-12 months; 60% vs 10% aged 12-24 months, P<0.001), requirement of parental intervention (82% vs 55% aged 3-12 months, P<0.05; 92% vs 55% aged 12-24 months, P<0.001), significantly delayed onset of sleeping through the night, and greater prevalence of daytime sleep beyond 24 months. Similar but less striking differences were seen comparing those with (n=76) and without GORD (n=26). CONCLUSIONS: Sleep interruption occurs more frequently in infants and children with GORD than population norms. Objective evaluation of infants and children with sleep disturbance after the age of 3 months may avoid unnecessary over or under diagnosis of GORD. Systematic investigation of the contribution of GORD to sleep disturbance in infants and young children is warranted.

Child, Preschool↗
PubMed1998

Nutritional management of regurgitation in infants.

Infantile regurgitation is a frequently occurring problem. Throughout the world, anxious parents are imploring physicians to eliminate their infant's regurgitation. General practitioners, pediatricians and pediatric gastroenterologists strive to alleviate infantile regurgitation and its related parental stress. In this paper we define the scope of the problem and analyze the optimal, cost-efficient management approach to simple regurgitation in infants. The intent of this paper is to disseminate this information to practicing physicians and other health care professionals in an attempt to minimize the impact of this annoying problem of infancy and to eliminate confusion and expensive diagnostic tests and use of sub-optimal treatment modalities. Parental reassurance and dietary management by feeding thickened formula are important components in managing regurgitation in infants while maintaining optimal nutritional intake for adequate growth and development.

Gastroesophageal Reflux↗
PubMed1998

Growth hormone resistance and somatomedins in children with end-stage liver disease awaiting transplantation.

BACKGROUND: The success of orthotopic liver transplantation as treatment for end-stage liver disease has prompted investigation of strategies to maintain or improve nutrition and growth in children awaiting transplantation, because malnutrition is an adverse prognostic factor. The purpose of this study was to evaluate the effect of recombinant human growth hormone therapy on body composition and indices of liver function in patients awaiting transplant. METHODS: The study was designed as a placebo-controlled, double-blind, crossover trial. Patients received 0.2 U/kg growth hormone, subcutaneously, or placebo daily for 28 days during two treatment periods, separated by a 2-week washout period. Ten patients (mean age, 3.06 +/- 1.15 years; range, 0.51-11.65 years, five men), with extrahepatic biliary atresia (n = 8) or two with Alagille's syndrome (n = 2), with end-stage liver disease, completed the trial while awaiting orthotopic liver transplantation. Height, weight, total body potassium, total body fat, resting energy expenditure, respiratory quotient, hematologic and multiple biochemical profile, number of albumin infusions, insulin-like growth factor-1 and 1, growth hormone binding protein (GHBP), and insulin-like growth factor binding protein-1 (IGFBP-1) and insulin-like growth factor binding protein (IGFBP-3) were measured at the beginning and end of each treatment period. RESULTS: Growth hormone treatment was associated with a significant decline in serum bilirubin (-34.6 +/- 16.5 mumol/l vs. 18.2 +/- 11.59 mumol/l; p < 0.02) but there was no significant effect on any anthropometric or body composition measurements, or on any biochemical or hematologic parameters. CONCLUSIONS: These children with end-stage liver disease displayed growth hormone resistance, particularly in relation to the somatomedin axis. Exogenous growth hormone administration may be of limited value in these patients.

Bilirubin↗
PubMed1997

Evaluation of bioelectrical impedance for prospective nutritional assessment in cystic fibrosis.

We have compared the use of bioelectrical impedance analysis (BIA) with anthropometry for the prediction of changes in total body potassium (TBK) in a group (n = 31) of children with cystic fibrosis. Linear regression analysis showed that TBK was highly correlated (r > 0.93) with height2/impedance, weight, height, and fat-free mass (FFM) estimated from skin-fold measurements. Changes in TBK were also correlated, but less well, with changes in height2/impedance, weight, height, and FFM (r = 0.69, 0.59, 0.44, and 0.40, respectively). The children were divided into two groups: those who had normal accretion of TBK (> 5%/y) and those who had suboptimal accretion of TBK (< 5%/y). Analysis of variance showed that the significant difference in the change in TBK between the groups was detectable by concomitant changes in impedance and weight but not by changes in height, FFM, or weight and height Z scores. The results of this study suggest that serial BIA measures may be useful as a predictor of progressive undernutrition and poor growth in children with cystic fibrosis.

Adolescent↗
PubMed1997

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.

Adolescent↗
PubMed1996

Resting energy expenditure, pulmonary inflammation, and genotype in the early course of cystic fibrosis.

To further investigate the early course of cystic fibrosis (CF), specifically to examine factors contributing to energy imbalance, we examined resting energy expenditure (REE) (by indirect calorimetry) per unit body weight and metabolically active body cell mass (by total body potassium), in relation to CF genotype (by genomic DNA analysis), CF pancreatic phenotype, and markers of pulmonary inflammation (from bronchoalveolar lavage fluid). Eighteen subjects with presymptomatic CF who were less than 2 years of age (n = 11, delta F508/ delta F508 genotype; n = 15, pancreatic insufficiency phenotype), identified by newborn screening, were compared with age-, sex-, and length-matched control subjects (n = 13). Those with the delta F508/ delta F508 genotype had significantly higher mean REE expressed per unit body weight (125%) and body cell mass (115%; p < 0.03). Those with other genotypes (n = 7) did not, as a group, have significantly different mean REEs, but individuals with known "severe" genotypes had REEs in the high range and those with a pancreatic-sufficient phenotype had significantly lower REE than those with a pancreatic-insufficient phenotype (p < 0.05), and REEs were in the normal range. Examination of bronchoalveolar lavage fluid revealed positive culture results (7/10) but variable colony counts, neutrophil percentages, and concentrations of interleukin-8 and interleukin-1 beta equally in both CF genotype groups. These markers of pulmonary inflammation were not correlated, individually or collectively, with REE or genotype. We conclude that genotypic variations in energy balance are detectable early in CF unrelated to lung inflammation. Subclinical defects in body composition and pulmonary integrity occur early in CF and, in combination with increased cellular metabolic activity, have important clinical implications with respect to early diagnosis and management.

Body Composition↗
PubMed1996

Pre- and postoperative nutritional care in liver transplantation in children.

Orthotopic liver transplantation (OLT) is now a definitive treatment option for most cases of endstage liver disease (ESLD) in children. Efforts now focus on active supportive treatment to maintain, if not improve, the patient's clinical status before OLT and to ensure normal patterns of growth and development after OLT. Malnutrition adversely affects the outcome of OLT and is probably the single area in pre-operative management where the largest potential improvement can be made. Our studies indicate significant abnormalities of protein energy metabolism and body composition in children referred for OLT. We have shown that the use of enteral formulae, enriched with branched-chain amino acids, have significant advantages. Other adjunctive therapy, such as growth hormone, is the subject of current investigation. Following transplantation, catch-up weight and growth does occur with the advent of normal liver function, but patients at continuing risk for undernutrition, such as those with rejection and/or chronic infection, need to be targeted for specific nutritional therapy.

Child↗
PubMed1995

Biological and genetic analysis of a longitudinal collection of Giardia samples derived from humans.

Duodenal aspirates from children investigated for diarrhoea have been examined for the presence of Giardia over an eleven year period, and where possible, in vitro or in vivo Giardia cultures in mice were established. Based on biochemical characteristics of electrophoretic karyotype, RFLP analysis and rDNA hybridization studies of 40 stocks at least two major varieties, or demes, of Giardia have infected the population of South East Queensland and environs during this period. These demes carried different rDNA repeat units and differed markedly in both the electrophoretic karyotype pattern and the molar representation of chromosome bands. From 1983 to 1991 only one deme was documented. The first evidence of a new deme seen in local children occurred in 1991 and was followed by a predominance of this deme in 1993. These 40 stocks do not represent all positive samples. Other stocks established in vivo were not able to be cultured in vitro, and these probably represent other demes. Since all of the stocks established in vivo were not able to be cultured in vitro, and these probably represent other demes. Since all of the stocks were derived from children with similar chronic symptoms it appears that at least two demes of Giardia are pathogenic.

Animals↗
PubMed1995

Measured versus predicted resting energy expenditure in infants: a need for reappraisal.

The reliability of commonly used predictive equations for estimating energy expenditure in infants in both health and disease was assessed by comparing resting energy expenditure (REE, measured by indirect calorimetry) in relation to weight, height, and body cell mass (by total body potassium analysis) with predictive equations (Harris-Benedict, Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU), Schofield weight-only, and Schofield weight-and-height equations) in 36 healthy infants (age 0.43 +/- 0.27 years; 19 male) and in 9 infants with cystic fibrosis (age 0.41 +/- 0.30 years; 4 male). Mean +/- SD REE for healthy boys was 0.205 +/- 0.019 MJ kg-1 day-1 and for healthy girls 0.217 +/- 0.026 MJ kg-1 day-1. Infants with cystic fibrosis had a significantly higher REE (0.258 +/- 0.034 vs 0.210 +/- 0.024 MJ kg-1 day-1; p < 0.005). Compared with measured values, predicted REE values varied markedly among equations, overestimating REE in healthy infants (Harris-Benedict equation, 182% +/- 63% (SD) of measured values; FAO/WHO/UNU equation, 104% +/- 14%; Schofield weight-only equation, 107.5% +/- 14%; and Schofield weight-and-height equation, 106% +/- 11%) and underestimating REE in those with cystic fibrosis (84% to 88% for the FAO/WHO/UNU, Schofield weight-only, and Schofield weight-and-height equations) except the Harris-Benedict equation (152%). On regression analysis both weight and body cell mass were related significantly to REE (r2 = 0.87 and r2 = 0.61, respectively) for normal infants and (r2 = 0.92 and r2 = 0.94) for those with cystic fibrosis. Using a generalized linear model of variance, we saw a significant (p < 0.001) variability among all REE measures. Thus we could rely on none of the predictive equations to give an accurate estimate of REE, and hence energy and fluid requirements, in individual infants. We suggest that when accurate estimates are needed, measurement of REE in individual infants should be attempted, especially in disease states, and that the continued use of current formulas should be reexamined.

Body Composition↗
PubMed1995

Multiple frequency bioelectrical impedance for the prediction of total body potassium in cystic fibrosis.

The use of multiple frequency bioelectrical impedance analysis (MFBIA) was compared with single frequency bioelectrical impedance analysis (SFBIA) and anthropometry to estimate the size of the body cell mass (BCM) in a paediatric cystic fibrosis population. BCM was independently determined from the accepted gold standard reference of total body potassium (TBK). MFBIA was used to measure the impedance of the body at 248 frequencies from 4 kHz to 1 MHz. Data were analysed using Cole-Cole plots of reactance versus resistance. The limits of agreement procedure was used to determine the reliability and precision of the different techniques to predict values for TBK, in an individual subject. The results indicate that MFBIA with a precision of 12% offers little improvement over single frequency BIA but is better and more accurate than anthropometry for the prediction of TBK in an individual patient.

Journal Article↗
PubMed1994

Persistent wheezing and gastroesophageal reflux in infants.

We have evaluated the presence of gastroesophageal reflux (GER) and the effect of its treatment in 12 infants (mean age, 7 months; range, 4-11 months) with persistent wheezing not responding to bronchodilators and anti-inflammatory asthma medications. All patients had GER on cineradiography and significant acid reflux on 24 hour pH monitoring (percentage of time pH < 4 ranged from 6.1 to 47%). All infants were initially treated with prokinetic agents and with receptor histamine antagonists in addition to aggressive pulmonary therapy. Six patients treated medically had substantially decreased use of asthma medications, completely discontinuing them within 2-4 months. Two patients, though significantly improved, require intermittent asthma therapy. Four patients responding poorly to GER and asthma treatment for 2 months to 2 years had fundoplications. These had an excellent outcome over 1-4.5 years follow-up; only one patient required further asthma medications. Pulmonary function testing was done in six patients before and after 6-8 weeks of therapy indicating significant improvement in peripheral airflow: terminal flow/peak tidal expiratory flow (TEF25/PTEF), and percentage of total expiratory time to reach peak tidal expiratory flow (Tp/Te or Tme/Te). Our experience suggests that evaluation for GER should be considered in infants with persistent wheezing. Aggressive medical and possibly surgical therapy for GER may resolve persistent wheezing.

Anti-Inflammatory Agents↗
PubMed1994

The management and long-term results of Japanese pediatric liver transplant recipients.

We investigated the long-term results and ongoing management issues of 39 Japanese children who underwent liver transplantation in Brisbane, Australia. Whole liver grafts were used in 15 patients (Wh group) and reduced-size grafts were used in 24 patients (Re group). The 1-year and 3-year survival rates were 74% and 60%, respectively, and all cases of late mortality which occurred after 6 months were due to infection. Statistical analysis showed no differences between the Wh and Re groups with regard to late mortality or liver function tests, although 4 of 24 (16.7%) patients from the Re group developed a recurrence of esophageal varices. Three patients treated with cyclosporine developed lymphoproliferative disorders following transplantation, but none of the patients developed severe nephrotoxicity or hypertension. Although a "catch-up" gain in weight was observed, poor growth in height was displayed, and there were no differences between the Wh and Re groups in this regard. Thus, we conclude that late complications of liver transplantation in children are common and further studies are necessary to evaluate the ongoing growth problems.

Australia↗
PubMed1994

Body composition in nonalcoholic cirrhosis: the effect of disease etiology and severity on nutritional compartments.

BACKGROUND/AIMS: Previous studies of body composition in cirrhosis have either measured only one body compartment, used alcoholic subjects, or not corrected body composition for physical characteristics. The aim of this study was to perform a detailed analysis of body composition in subjects with nonalcoholic cirrhosis. METHODS: Simultaneous measurements of total body potassium and total body water were performed and values of body cell mass and body fat were corrected for physical characteristics. RESULTS: Child's class C patients had a significantly lower mean total body potassium index (i.e., percent observed value/expected value) and body fat index than class A or B patients. Eighty-one percent of class C patients had simultaneous reductions in body fat and body cell mass, and 71% of patients with class A disease had a significant reduction in either or both compartments. Nine patients showed the pattern of tissue loss seen with short-term starvation. Fourteen patients showed the pattern of tissue loss seen in physiological stress. CONCLUSIONS: Severe liver disease is characterized by significant reductions in body fat and body cell mass, most class A patients have a significant reduction in some nutritional compartments, and the pattern of tissue loss may reflect mechanisms of tissue wasting.

Adipose Tissue↗
PubMed1994

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↗