Biomedical subjects

P G Lunn

Publications and source records attributed to P G Lunn.

At least 19 recordsLinked to original sources

PubMed2003

Growth faltering in rural Gambian infants is associated with impaired small intestinal barrier function, leading to endotoxemia and systemic inflammation.

Growth faltering of rural Gambian infants is associated with a chronic inflammatory enteropathy of the mucosa of the small intestine that may impair both digestive/absorptive and barrier functions. The aim of this study was to determine whether the enteropathy was associated with a compromised barrier function that allowed translocation of antigenic macromolecules from the gut lumen into the body, with subsequent systemic immunostimulation, resulting in growth retardation. Rural Gambian infants were studied longitudinally at regular intervals between 8 and 64 wk of age. On each study day, each child was medically examined, anthropometric measurements were made, a blood sample was taken and an intestinal permeability test performed. Evidence of chronic immunostimulation was provided by abnormally elevated white blood cell, lymphocyte and platelet counts, and frequently raised plasma concentration of C-reactive protein. Intestinal permeability was abnormal and associated with impaired growth (r = -0.41, P < 0.001). Plasma concentrations of endotoxin and immunoglobulin (Ig)G-endotoxin core antibody were also elevated and related to both growth (r = -0.30, P < 0.02; r = -0.64, P < 0.0001, respectively) and measures of mucosal enteropathy. Plasma IgG, IgA and IgM levels increased rapidly with age toward adult concentrations. Raised values were related to poor growth but also to measures of mucosal enteropathy and the endotoxin antibody titer. The interrelationships among these variables and growth suggested that they were all part of the same growth-retarding mechanism. These data are consistent with the hypothesis of translocation of immunogenic lumenal macromolecules across a compromised gut mucosa, leading to stimulation of systemic immune/inflammatory processes and subsequent growth impairment.

Body Height↗

PubMed2003

Early results of the Souter-Strathclyde unlinked total elbow arthroplasty in patients with osteoarthritis.

We have carried out a retrospective review of 11 Souter-Strathclyde primary total elbow arthroplasties in ten patients with osteoarthritis, over a period of nine years. The diagnosis was primary osteoarthritis in nine elbows and post-traumatic arthritis in two. The mean follow-up was 68 months (15 to 117). Although no patient was symptomatic, radiological review revealed evidence of loosening affecting three humeral and two ulnar components, one of which subsequently failed and was revised at 97 months. There were no dislocations, deep infections or mechanical failures. Complications included two superficial wound infections and two neurapraxias of the ulnar nerve which resolved. This study shows that the unlinked Souter-Strathclyde total elbow arthroplasty can be considered for patients with osteoarthritis and gives good symptomatic relief and improvement in function.

Aged↗

PubMed2001

Elevated acute-phase protein in stunted Nepali children reporting low morbidity: different rural and urban profiles.

This study examined the associations between severity of stunting, plasma protein concentrations and morbidity of 104 Nepali boys, aged 10-14 years, living in contrasting environments. Boys from a remote village were compared with three similarly aged urban groups: poor squatters, homeless street children, and middle-class schoolchildren. All but the middle-class group were stunted, particularly village boys whose mean height-for-age z-score (-2.97, SD 0.82) indicates severe growth retardation. Stunting was significantly associated with increased plasma levels of the acute-phase protein alpha1-antichymotrypsin itself inversely related to plasma levels of albumin. Plasma ACT levels of village children (mean 1.52 g/l, SD 0.43) were three to four times higher than those of squatters and homeless street children, and five times higher than those of middle-class boys. Despite being the most severely stunted and having the most abnormal plasma protein values, village children reported the lowest burden of disease, a contradiction which may reflect exposure to sub-clinical infections or habituation to illness and low expectation of treatment. This study draws attention to the strikingly high levels of ACT and of stunting in the rural sample, and cautions on the use of uncorroborated morbidity reports across different epidemiological and socio-ecological environments. Possible mechanisms to explain the impact of illness and inflammation on growth faltering are discussed.

Acute-Phase Proteins↗

PubMed2001

Anthelmintic treatment of rural Bangladeshi children: effect on host physiology, growth, and biochemical status.

BACKGROUND: The effect of helminth infestation on the nutrition, growth, and physiology of the host is still poorly understood. Anthelmintic treatment of children in developing countries has had varying success in terms of growth improvements. OBJECTIVE: The objective of this study was to assess the effect of regular deworming on child growth, physiology, and biochemical status. DESIGN: The study was a 12-mo longitudinal intervention in 123 Bangladeshi children aged 2-5 y. Treatment (mebendazole) or placebo tablets were administered every 2 mo for 8 mo and again at 12 mo. Weight, height, midupper arm circumference, intestinal permeability, plasma albumin, alpha(1)-antichymotrypsin, and total protein concentration were assessed every 2 mo. RESULTS: Treatment with mebendazole reduced the prevalence of Ascaris lumbricoides from 78% to 8%, of Trichuris trichiura from 65% to 9%, and of hookworm from 4% to 0%. There was no significant difference in the growth of treated children compared with those given placebo tablets. No changes in intestinal permeability or plasma albumin were observed after deworming. Significant decreases in total protein (P<0.001) and alpha(1)-antichymotrypsin (P<0.001) were observed in the treatment group, indicating possible reductions in inflammation and immunoglobulin concentration after deworming. A significant increase in the prevalence of Giardia intestinalis (from 4% to 49%) in the treatment group was associated with a short-term reduction in weight (P = 0.02) and higher intestinal permeability (P <0.001) in infected subjects. No long-term effects of G. intestinalis on growth were observed. CONCLUSION: Low-intensity helminth infections, predominantly of A. lumbricoides and T. trichiura, do not contribute significantly to the poor growth and biochemical status of rural Bangladeshi children.

Animals↗

PubMed2000

The impact of infection and nutrition on gut function and growth in childhood.

Poor growth performance during infancy and early childhood is a frequent fact of life in most developing countries. Work in The Gambia has demonstrated that more than 43 % of observed growth faltering during the first 15 months of life can be explained by the presence of a mucosal enteropathy in the small intestine. Within communities the illness is very common: in the area investigated more than 95 % of infants above 8 months of age were affected, and on average they suffered a growth-limiting enteropathy for more than 75 % of their first year of life. Two mechanisms of weight loss have been defined. First, partial villus atrophy reduces absorption and digestion of lactose and probably other nutrients. Second, and more importantly, damage to the mucosal barrier allows translocation of macromolecules into the mucosa and blood, triggering both local and systemic immune and inflammatory mechanisms. Given the severity of the enteropathy it is not surprising that infants fail to grow at a normal rate. Recent findings suggest that these lesions continue throughout childhood and into adulthood. Thus, a persistence of chronic, local and systemic inflammation throughout childhood may be responsible for continued poor growth during this period. Although the nature of the enteropathy and the mechanisms of growth failure have been defined, the factors involved in the initiation and persistence of the intestinal lesion remain uncertain, making clinical management difficult. More work is clearly required to elucidate these factors and to define interventions to prevent or treat the enteropathy.

Gambia↗

PubMed2000

Innate immunity, gut integrity, and vitamin A in Gambian and Indian infants.

Gut integrity, which can be measured by the urinary lactulose:mannitol excretion test, deteriorates with the introduction of weaning foods. In The Gambia, gut integrity measured monthly over 15 months in 119 infants (aged 2-15 months) was least impaired from April to June. This coincides with the time of year of maximum vitamin A (VA) intake-the mango season. Subsequently, two VA intervention studies were done in infants in India. Eighty infants attending a community health center received 16,700 IU weekly or placebo. In another study, 94 hospitalized infants were given 200, 000 IU VA or placebo: 31 received VA on admission, while the rest (32 VA, 31 placebo) received treatment on discharge. All VA-treated groups had more rapid improvement in gut integrity than the placebo groups, but no group had gut integrity normalized by Western standards. The data suggest that VA status may influence gut integrity.

Child, Hospitalized↗

PubMed1999

Giardia intestinalis is unlikely to be a major cause of the poor growth of rural Gambian infants.

Parasite-specific plasma immunoglobulins have been used to indicate the presence of Giardia intestinalis infection in 60 infants living in a rural area of The Gambia. Infants were studied longitudinally between 2 and 8 mo of age. The median age for first exposure to G. intestinalis was between 3 and 4 mo, and by 8 mo all but 3 infants (95%) showed a positive titer on at least one occasion. Raised Giardia-specific IgM titers were associated with reduced weight gain in the 2 wk preceding a positive titer, but catch-up growth occurred in the following 2 wk. IgM antibody titers were also positively associated with intestinal permeability (lactulose/mannitol ratio), urinary lactose excretion, plasma concentrations of alpha1-antichymotrypsin and total IgM, IgA and IgG immunoglobulins. However, infant growth over the whole 6-mo period (i.e., between 2 and 8 mo of age) was not related to mean Giardia-specific antibody titers, nor the time of first exposure to the parasite. The data suggest that giardiasis in these very young breast-fed children occurs as a mild, acute disease, and its presence could not explain the marked, long-term growth faltering observed in many of the subjects.

Analysis of Variance↗

PubMed1999

Glutamine oxidation and utilization by rat and human oesophagus and duodenum.

The rates of utilization and oxidation of glutamine and glucose by oesophageal and duodenal tissues have been investigated in both rats and human subjects. In the rat, glutamine utilization by oesophageal tissue was 2-3-fold lower than that in the duodenum, and this substrate contributed less than 10% to the total oxidative metabolism of the tissue, even when glutamine was the only substrate provided. In contrast, rat duodenal tissue derived about 34% of the total CO2 production from glutamine-C, and this contribution was not suppressed by the addition of either glucose or a mixture of the other substrates. Rates of glucose utilization and oxidation by the duodenum were lower than those for glutamine, and were significantly (P < 0.001) suppressed by addition of glutamine. In both oesophageal and duodenal tissues, less than 10% of the glutamine-C utilized was fully oxidized, approximately 60-70% was converted to glutamate, and 30-40% to alanine. Results obtained using human biopsy tissue samples were similar to those observed in the rat. Glutamine oxidation contributed 34 (SD 4)% of the total CO2 production by the duodenal tissue, but only 8 (SD 4)% to oesophageal tissue oxidation. The findings suggest that glutamine is not an important or preferred fuel for oesophageal tissue, whereas it is for duodenal tissue. Thus, these tissues can be expected to respond differently to glutamine administration.

Analysis of Variance↗

PubMed1998

The treatment of selected fractures of the humeral shaft with the True-Flex nail.

The True-Flex nail was used in 23 selected non-pathological and eight pathological fractures/lesions of the humeral shaft. The overall fracture union rate was 69.5 per cent and the patients achieved a good range of movement of the shoulder and elbow. Nailing did not lead to union of established non-unions or fractures which were previously treated unsuccessfully by surgery despite bone grafting. All patients with pathological fractures/lesions regained good function of the arm and a good range of movement of the shoulder and the elbow. In one case the nail migrated proximally and impinged on the rotator cuff. This was revised. No other technical difficulties or complications were seen. The True-Flex nail is useful in the treatment of difficult and relatively recent humeral shaft fractures. Established non-unions or cases where previous surgery has failed should be treated by alternative methods.

Adult↗

PubMed1998

A case of kwashiorkor in the UK.

A case of kwashiorkor in a British child of Caucasian origin is described. The 5-year-old boy was referred to hospital for investigation of a persistent anaemia, but on examination was found to have classical features of kwashiorkor. He was stunted with both height and weight below the fifth centile and had mild pitting oedema in both legs. His hair was pale and easily pluckable and a soft liver edge was palpable. Plasma albumin concentration was 16 g/l and the plasma amino acid pattern, which revealed markedly reduced levels of essential but normal to high non-essential amino acids, was similar to that described in kwashiorkor in Uganda. A dietary history revealed that for about 2 years the child's diet had contained very little protein but adequate energy and had been supplemented with multivitamin pills. There was no evidence of other pathology, neglect or abuse and the child responded rapidly to refeeding with a balanced diet.

Amino Acids↗

PubMed1998

Distribution of glutaminase and glutamine synthetase activities in the human gastrointestinal tract.

1. The activities of the two key enzymes involved in glutamine metabolism, glutaminase and glutamine synthetase, were measured in mucosal biopsies taken from different sites throughout the human gastrointestinal tract, from oesophagus to rectum. 2. The specific activity of glutamine synthetase was highest in the stomach (4.5 nmol glutamine formed per minute per mg of protein), but both small and large intestine and the oesophagus had little synthesizing capacity (less than 0.3 nmol of glutamine formed per minute per mg of protein). 3. Glutaminase specific activity was highest in the small intestine (53 nmol glutamate formed per minute per mg of protein by duodenal mucosa), intermediate in the large intestine and lowest in the oesophagus and stomach (less than 13 nmol of glutamate formed per minute per mg of protein). 4. The glutamine concentration in the mucosa was lower in the duodenum than in the colon (0.62 and 0.95 mmol/kg wet weight respectively), but both were much lower than the measured K(m) values of glutaminases obtained from these sites (3.8 and 4.0 nmol/kg wet weight respectively). 5. The concentration of glutamine in saliva, stomach juice, bile and duodenal juice suggests that very little glutamine passes into the gastrointestinal tract via these secretions. 6. The study provides the most complete information on the distribution of glutamine synthetase and glutaminase along the human gastrointestinal tract, and suggests that (i) both the small and large intestines have a high potential for glutamine metabolism, but little synthesizing capacity, thus both must derive their glutamine from other sources, and (ii) neither the stomach nor the oesophagus have a high glutaminase activity, although the stomach has substantial capacity to synthesize glutamine. The distribution of the enzymes along the gastrointestinal tract may help rationalize the use of glutamine for treating diseases that affect different parts of the gastrointestinal tract.

Adult↗

PubMed1998

Glutamine metabolism in the gastrointestinal tract of the rat assess by the relative activities of glutaminase (EC 3.5.1.2) and glutamine synthetase (EC 6.3.1.2).

The activities of the two key enzyme involved in glutamine metabolism, glutaminase (EC 3.5.1.2) and glutamine synthetase (EC 6.3.1.2), have been measured in the various tissues of the gastrointestinal (GI) tract of the rat, from the mouth to the rectum. Glutaminase activity was particularly high in the mucosa of the small intestine, where its activity accounted for more than 80% of the total activity of the GI tract. In contrast, the mouth and oesophagus had very low activities, accounting for less than 2% of the total. Glutamine synthetase was mainly confined to the lower part of the stomach, which accounted for almost 90% of the total activity of the GI tract. Activity in the small intestine was very low, accounting for less than 2% of the total, and similarly low levels were found in the mouth and oesophagus. The data provide the most complete information on the distribution of these enzymes in the GI tract of the rat and suggest: (a) that the mucosa of the small intestine has the highest capacity for glutamine breakdown but the lowest capacity for its synthesis, and so requires an external source of this amino acid; (b) that there is little potential for glutamine synthesis or breakdown in the mouth and oesophagus: and (c) that the lower stomach has a substantial capacity to synthesize glutamine, in contrast to the rest of the GI tract. The results of the investigation are relevant to sites of glutamine metabolism in therapeutic studies involving glutamine administration discussed with reference to reports of the effects of glutamine administration on GI tract injury.

Animals↗

PubMed1998

Lowering of plasma triiodothyronine level and sympathetic activity does not alter hypoalbuminaemia in rats fed on a diet of low protein concentration.

Previous studies have described high plasma triiodothyronine (T3) concentrations and sympathetic activity in rats fed on low-protein diets. The present investigation examined how the nutritional status of rats fed on a low-protein diet was affected when these hormonal changes were reduced by drug administration. The low-protein diet (LP group) prevented growth, reduced plasma albumin levels, elevated plasma T3 concentration, and increased both the weight of the interscapular brown adipose tissue (BAT) and the activity of BAT cytochrome c oxidase (EC 1.9.3.1). Lowering the plasma T3 concentration (with carbimazole; CA group) elevated the plasma insulin concentration, promoted a small increase in the plasma albumin concentration and caused weight gain in comparison with the LP group. Reduction of sympathetic activity (with alpha-methyl-p-tyrosine; MT group) promoted a small elevation in plasma albumin concentration accompanied by a diminished T3 concentration, BAT weight, and an increase in fat deposition in relation to LP rats. In a second experiment, simultaneous lowering of the plasma T3 concentration and sympathetic activity (CA/MT group) resulted in weight gain associated with elevated plasma insulin concentration and fat deposition and a marked reduction in BAT cytochrome c oxidase activity. However no change in the hypoalbuminaemia was observed. The results of the present study suggest that in spite of the previously described increase in metabolic rate in fed on a diet with low-protein concentration when compared with controls, the mechanisms involved in the control of BAT activity and fat deposition seem to be independent of those which cause liver protein depletion and hypoalbuminaemia.

Adipose Tissue, Brown↗

PubMed1998

Increase in skeletal muscle protein content by the beta-2 selective adrenergic agonist clenbuterol exacerbates hypoalbuminemia in rats fed a low-protein diet.

This investigation examined how the nutritional status of rats fed a low-protein diet was affected when the animals were treated with the beta-2 selective agonist clenbuterol (CL). Males (4 weeks old) from an inbred, specific-pathogen-free strain of hooded rats maintained at the Dunn Nutritional Laboratory were used in the experiments (N = 6 rats per group). CL treatment (Ventipulmin, Boehringer-Ingelheim Ltd., 3.2 mg/kg diet for 2 weeks) caused an exacerbation of the symptoms associated with protein deficiency in rats. Plasma albumin concentrations, already low in rats fed a low-protein diet (group A), were further reduced in CL rats (A = 25.05 +/- 0.31 vs CL = 23.64 +/- 0.30 g/l, P < 0.05). Total liver protein decreased below the level seen in either pair-fed animals (group P) or animals with free access to the low-protein diet (A = 736.56 +/- 26 vs CL = 535.41 +/- 54 mg, P < 0.05), whereas gastrocnemius muscle protein was higher than the values normally described for control (C) animals (C = 210.88 +/- 3.2 vs CL = 227.14 +/- 1.7 mg/g, P < 0.05). Clenbuterol-treated rats also showed a reduction in growth when compared to P rats (P = 3.2 +/- 1.1 vs CL = -10.2 +/- 1.9 g, P < 0.05). This was associated with a marked decrease in fat stores (P = 5.35 +/- 0.81 vs CL = 2.02 +/- 0.16 g, P < 0.05). Brown adipose tissue (BAT) cytochrome oxidase activity, although slightly lower than in P rats (P = 469.96 +/- 16.20 vs CL = 414.48 +/- 11.32 U/BAT x kg body weight, P < 0.05), was still much higher than in control rats (C = 159.55 +/- 11.54 vs CL = 414.48 +/- 11.32 U/BAT x kg body weight, P < 0.05). The present findings support the hypothesis that an increased muscle protein content due to clenbuterol stimulation worsened amino acid availability to the liver and further reduced albumin synthesis causing exacerbation of hypoalbuminemia in rats fed a low-protein diet.

Adipose Tissue, Brown↗

PubMed1998

Protein deficiency in a colony of western lowland gorillas (Gorilla g. gorilla)

A syndrome of alopecia and weight loss in a colony of 10 western lowland gorillas (Gorilla gorilla gorilla) in Gabon during a 3-yr period was apparently due to a dietary protein deficiency, with nine individuals affected to some extent. The most severely afflicted was a 4-yr-old female who eventually died as a result of acute gastroenteritis caused by Shigella flexneri. Clinical signs included chronic alopecia, hair discoloration, failure to thrive, and weight loss, and their severity was directly correlated with the degree of hypoalbuminemia (12 g/L in the most extreme case) and normocytic normochromic anemia. Preliminary clinical tests and autopsy results suggested a dietary protein or amino acid deficiency as the cause of the hypoalbuminemia, and further analyses of serum amino acid and protein levels were consistent with a diagnosis of dietary protein deficiency. Supplementation of the colony diet with a protein preparation for humans produced a rapid amelioration of signs and improvement in body and coat condition, a normalization of serum albumin and total protein levels, and disappearance of the anemia in all affected animals except a 12-yr-old male, who responded well to treatment with anabolic steroids. The natural diet of western lowland gorillas is surprisingly high in protein, and the dietary protein requirement of captive gorillas may be increased as a result of the absence of commensal gastrointestinal ciliates.

Alopecia↗

PubMed1998

Maternal reports of child illness and the biochemical status of the child: the use of morbidity interviews in rural Bangladesh.

In a longitudinal study of child growth and nutritional status in Bangladesh, child morbidity was recorded using health interviews with the mother. The aim of the present study was to establish whether maternal reports of child illness were associated with the biochemical health status of the child. Children aged 2-5 years (n 117) took part in the study and their mothers were interviewed every fortnight by Bangladeshi fieldworkers. Maternal reports of diarrhoea were associated with significantly lower plasma albumin concentrations (P < 0.001), poorer intestinal permeability (P < 0.001), higher plasma immunoglobulin A levels (P < 0.005) and higher alpha-1-antichymotrypsin (ACT) levels (P < 0.05) compared with children reported to be healthy. Children with fever had significantly higher ACT (P < 0.001) and lower albumin (P < 0.05) levels compared with their healthy counterparts. Respiratory infections (RI) were not associated with any significant changes; however, reports of RI with fever were associated with significantly higher levels of ACT than either illness individually (interaction P < 0.05). These highly significant associations between maternal reports of illness and biochemical profiles of child health support the use of health interviews in developing countries.

Albumins↗

PubMed1997

Biological markers of protein-energy malnutrition.

The biological markers of undernutrition fall into three categories: (a) those that measure structure; (b) those that measure function; and (c) indices of the above two. Ideally a marker of nutritional status should have the following characteristics: specific to nutritional status; sensitive to changes in nutritional status; reproducible; simple to measure; inexpensive and widely available. Unfortunately there are no such markers, and therefore individuals involved in the assessment of nutritional status should be aware of the advantages and disadvantages of the markers they use. For example, body composition can be assessed using sophisticated techniques that make fewer assumptions than simple bedside techniques (1). However, these sophisticated techniques (eg neutron activation, and combinations of techniques such as hydro-densitometry, water dilution techniques and dual-energy X-ray absorptiometry) are not widely available and some of them are labour intensive. On the other hand simple bedside techniques, such as those based on skinfold thicknesses can be applied widely because they are easy and quick to perform, but they are probably not as accurate as the classic body composition techniques (hydro-densitometry or water dilution techniques) or other sophisticated methods based on the assessment of multiple body compartments (1). Therefore the choice of method depends not only on the availability of investigative tools, but also on the practicalities of using them in individuals, a small group of individuals, or large groups of individuals, (eg national surveys during famine and non-famine conditions). In this brief review only some aspects concerned with simple bedside or laboratory methods will be discussed.

Journal Article↗

PubMed1997

Trapeziectomy alone, with tendon interposition or with ligament reconstruction?

This randomized prospective study compared the results of trapeziectomy alone, or combined with tendon interposition or ligament reconstruction in 76 women with basal thumb osteoarthritis. At 3 month and 1 year follow-up the results of the three procedures were indistinguishable in terms of pain relief, hand function and thumb strength. In the short term at least, tendon interposition and ligament reconstruction do not improve the results of trapeziectomy.

Female↗