PubMed Health⌕ Search

Biomedical subjects

A Wesley

Publications and source records attributed to A Wesley.

At least 19 recordsLinked to original sources

Effects of the human immunodeficiency virus on tuberculosis in children.

SETTING: Human immunodeficiency virus (HIV) infection has altered the epidemiological and clinical profile of tuberculosis (TB) worldwide. In children however, unlike in adults, very little has been documented about the interaction between the two diseases. OBJECTIVE: To examine the clinical features and response to TB treatment in children with TB and HIV, and compare them with those with TB alone. DESIGN: A prospectively enrolled case study with systematically selected controls was conducted between 1992 and 1994 at King George V tuberculosis hospital, in Durban. Forty children with TB and HIV (Group A) were compared with 40 children with TB alone (Group B). The diagnosis of TB was made in accordance with established criteria. Measures of comparison between the groups included: history of contact with a TB case, clinical presentation on admission, presence of bacille Calmette-Guérin (BCG) scar, reaction to tuberculin test, clinical response to anti-tuberculosis treatment (mean weight gain per month, improved appetite, resolution of chest signs, decreasing size of visceromegaly), radiological response to treatment (assessed according to an objective score on admission, at 6 months and on discharge), other associated diseases, nosocomial infections and survival. RESULTS: The mean age of the children in Group A was 25 months and in Group B 31 months. The clearest differences between the groups on admission were clinical features and response to tuberculin testing. Group A were more frequently anergic to tuberculin testing (P < 0.0001) and more often had symptoms and signs suggestive of TB (P = 0.002). Clinical response to treatment on discharge was worse in Group A than in Group B (P = 0.005). Radiological response to treatment at six months and on discharge was poorer in Group A than in Group B (P = 0.46; P = 0.006, respectively). Six children in group A and none in group B died (P = 0.012). The mean duration of treatment (and therefore period until discharge) was 8.9 months in Group B and 8.5 months in Group A for those who survived. History of contact, evidence of BCG inoculation and nosocomial infections were similar in both groups. CONCLUSION: HIV infection adversely affects the outcome of TB in children as assessed by response to treatment and survival.

AIDS-Related Opportunistic Infections↗

Clinical features of individuals with cystic fibrosis in New Zealand.

AIMS: To determine the status of cystic fibrosis patients, their mode of diagnosis and source of medical care in New Zealand. METHODS: A database was established in 1988 to record clinical information on individuals with cystic fibrosis in New Zealand. Three hundred and two cystic fibrosis patients were identified and clinical information on 248 obtained. RESULTS: Thirty five per cent of patients at diagnosis had gastrointestinal and pulmonary and 33% had gastrointestinal symptoms alone. Ninety three infants were diagnosed after a positive screening test and confirmatory sweat test. The mean age at diagnosis overall was 1.8 years, while 61% of children were diagnosed before one year of age. 74.2% of patients were said to be pancreatic insufficient, 4% pancreatic sufficient and in 22% the results were unavailable or unknown. Medical care was provided by 28 sources comprising paediatricians, physicians or combined clinics. One cystic fibrosis clinic cared for more than 40 patients. Sixty-one per cent of cystic fibrosis subjects were colonised with Staphylococcus aureus at some time, and 44% were reported to be colonised with Pseudomonas aeruginosa. CONCLUSIONS: Common clinical features of cystic fibrosis have been characterised for New Zealand patients. It is unknown to what extent the clinical features of the disease and source of medical care in New Zealand are responsible for previously reported survival for the condition but it is planned to examine serial measurements of growth, nutrition, pulmonary function and survival and it is hoped that these measurements will be the subject of a further report.

Adolescent↗

Determination of theophylline clearance in South African children.

Theophylline clearance values in South African children were determined using 400 serum theophylline concentration measurements gathered from 109 compliant outpatients during their normal routine care. Population pharmacokinetic analysis was done using the Non-Linear Mixed Effects Model (Nonmem) to analyse the data. Nonmem was also used to estimate the influence of fixed effects (weight, age, race, gender etc) on clearance and its interindividual variability. Gender, age, and weight raised to an iterated exponent were found to be the most important demographic fixed effect parameters influencing clearance. Race was not found to be important. The weight-adjusted values of theophylline clearance decreased with increasing age. The actual values expressed in l.h-1.kg-1 were 0.0949 for children aged 1-5 y; 0.0813 for children aged 5-9 y, and 0.0660 for children of 9-16 y. The values are similar to those reported in other studies.

Adolescent↗

Nosocomial colonisation and infection in a paediatric respiratory intensive care unit.

A study of the prevalence of nosocomial colonisation and nosocomial infection (NI) was conducted in the paediatric respiratory intensive care unit of a large teaching hospital serving a developing community. Surveillance specimens were collected regularly from 63 consecutive patients admitted over 4 months, and also from professional staff, boarder mothers, cleaners and the unit environment. The incidence among patients of colonisation (40%) and of NI (43%) was high. The risk of dying in children with NI was appreciably increased (relative risk 2,241, confidence interval 0,591-8,503). This did not reach statistical significance, probably because so few children escaped acquiring hospital organisms. The significant risk factor for acquiring colonisation (P = 0.008) and NI (P < 0.0001) was a ward stay of more than 10 days. In addition, for acquiring NI an age of under 6 months was also predictive (P = 0.0298). The nature of the primary illness dictated the time spent in the ward; an important proportion of patients had preventable diseases, such as measles, pneumonia and tetanus, which required prolonged treatment. All children with endotracheal intubation had hospital-acquired organisms in tracheal aspirates. Eighty-two per cent of children developed positive gastric aspirates, 17% a positive urine culture and 11% a positive blood culture. Colonisation occurred rapidly; organisms initially appeared in gastric aspirates (mean 2 days), then in tracheal aspirates (mean 5 days) and urine cultures (mean 10 days). The acquired organisms, many of which were antibiotic-resistant, were almost exclusively enteric Gram-negative bacilli (GNB) and Staphylococcus aureus.(ABSTRACT TRUNCATED AT 250 WORDS)

Cross Infection↗

Neutral and acidic species of human intestinal mucin. Evidence for different core peptides.

Highly purified human mucins from postmortem intestinal tissue were fractionated on anion exchange columns to generate separate neutral and acidic species. The neutral mucin (less than 1.0 mol % sialic acid) was the major species (greater than 80% by weight) and contained a higher molar proportion of fucose, galactose, and N-acetylglucosamine, and a lower proportion of sialic acid and N-acetylgalactosamine than the acidic species (greater than 10 mol % sialic acid). Amino acid analyses revealed a highly significant enrichment in serine, aspartate, and alanine in the neutral species and proline, threonine, and glycine in the acidic species. Thiol reduction of each species to remove their integral 118,000-dalton component did not alter the essential interspecies differences. Differences in threonine, proline, and serine also remained after removal of all "naked" or pronase-susceptible peptide regions from each species. These results indicate that neutral and acidic mucins contain glycopeptide segments exclusive of their 118,000-dalton and naked peptide components, which differ in amino acid composition. The key amino acid markers are similar to those observed for fuco- and sialoglycopeptides obtained after proteolytic digestion of human colonic mucin by Gold et al. (Gold, D.V., Schochat, D., and Miller, F. (1981) J. Biol. Chem. 256, 6354-6358). The oligosaccharide composition of small intestinal and colonic mucin may therefore depend upon transcriptional control of the synthesis of specific mucin peptides as well as the post-translational activity of glycosyltransferases. These findings may have significance for the quality and functions of mucus produced in a variety of pathological states.

Amino Acids↗

Sequential disaccharidase loss in rat intestinal blind loops: impact of malnutrition.

We studied lactase, maltase, and sucrase activities in the mucosa of self-filling blind loops (SFBL) in adult rats at weekly intervals after SFBL formation in order to determine the sequence in which disaccharidase activities fall. The studies were carried out on nourished and malnourished rats and extended to a recovery period induced by antibiotics to determine the effects of malnutrition on the establishment and repair of disaccharidase deficiencies caused by bacterial overgrowth. Malnutrition was produced by feeding 50% of the intake of paired rats fed ad libitum. Disaccharidase activities were determined in SFBL from nourished and malnourished rats at 7-day intervals until pandisaccharidase deficiency was established and during a 2-wk recovery period induced by antibiotics. Maximal SFBL bacterial counts in both nourished and malnourished groups of rats and brush-border glycoprotein degradation ratios were established at 7 days. In nourished rats only lactase was deficient at 7 days; maltase and sucrase fell later and sequentially. In malnourished rats all three disaccharidases were reduced at 7 days. Disaccharidase activities in self-emptying blind loops (SEBL), used as operated controls, were not decreased 28 days after surgery. Malnutrition had no effect on disaccharidase activities in the SEBL, and malnutrition did not affect recovery rates with antibiotic therapy. We conclude that small intestinal bacterial overgrowth causes a staggered loss of disaccharidase activities beginning with the loss of lactase activity. In the presence of bacterial overgrowth, malnutrition accelerates the conversion of a mono- to a pan-disaccharidase deficiency.

Animals↗

The metabolic response and problems with nutritional support in acute tetanus.

Thirteen patients with severe tetanus were studied in the first and second week of illness in order to assess metabolic changes and nutritional requirements. Nine required muscular paralysis and subsequent assisted ventilation in order to control spasms. Symptoms and signs of sympathetic overactivity were especially common in the latter groups with a fourfold increase in urinary adrenaline and noradrenaline excretion. Other hormonal and metabolic abnormalities included hyperglycemia, mildly elevated insulin concentrations with no significant rise in cortisol, and glucagon. Evidence of excessive protein catabolism was obtained particularly during the second week of illness, mean urinary nitrogen excretion being 20.5 +/- 13.8 g/d. Maintenance of nutrient homeostasis proved impossible with conventional enteral-feeding techniques: high-density feeds exacerbated hyperglycemia and diarrhea; low-density feeds were unable to maintain nitrogen balance (-12.34 g/d in ventilated patients, second week). The results indicate that loss of lean body mass is inevitable in such patients unless the metabolic response can be suppressed or more aggressive forms of nutritional support (eg, total parenteral nutrition including sufficient insulin to maintain normoglycemia) are employed.

Acute Disease↗

Abnormal mucus: nominated but not yet elected.

Mucus secretions of the intestine may contribute to plug formation in CF, through several mechanisms acting alone or simultaneously. Excessive mucin secretion and relative dehydration of secretions would elevate mucin concentration and enhance mucus gel formation. Deficient pancreatic enzymes combined with intrinsic hyperglycosylation of mucin or an increase in covalently bound fatty acid groups on mucins, would retard normal proteolytic degradation of mucins. Excessive calcium ions in the ducts would tend to decrease mucin solubility, while excessive hydrogen ions and protein (especially albumin) together with mucins, may be responsible for the appearance of proteinaceous ductal 'plugs' characteristic of CF pathology.

Albumins↗

Human intestinal mucin in cystic fibrosis.

Human intestinal mucins from six subjects with Cystic Fibrosis (CF) and eight subjects without CF were prepared from tissue obtained at surgery (one case) and postmortem. Subjects were not age-matched, but the nonCF mucin was obtained from subjects with ages which bracketed those of the CF subjects. Cesium chloride analytical gradient ultracentrifugation showed that CF mucins were generally denser than nonCF mucins. Sedimentation coefficients were also higher in the CF samples. CF mucins were enriched in fucose, galactose, N-acetylglucosamine and total carbohydrate per mg protein and per oligosaccharide chain (mole/mole GalNAc). Fucose/sialic acid molar ratios were significantly higher in CF mucins, and the average oligosaccharide chain length was approximately three residues greater in CF as compared with nonCF mucins. There was no difference in amino acid profiles or the number of side chains per molecule. The mean sulfate content was higher in the CF mucins but not to a level of significance; however, in the eight mucins, sulfate content correlated positively with total carbohydrate, N-acetylglucosamine and galactose, and therefore increased with oligosaccharide chain length. CF intestinal mucin was therefore denser and more highly glycosylated than nonCF musin and probably contained more sulfate. The increase in glycosylation resulted from a rise in fucose, galactose, and N-acetylglucosamine without a concomitant rise in sialic acid.

Acetylglucosamine↗

Clinical aspects of gastrointestinal mucus.

In such a bird's eye view of a very complicated and complex literature it is inevitable that significant contributions, particularly from earlier investigators, will have been overlooked. We have tried, however, to provide a reasonable framework for the many presentations and discussions which will take place at this conference. As in the past, it is evident that much needs to be done to reconcile the excellent histochemical studies of gastrointestinal mucus in many diseases with the increasing knowledge of mucin structure and composition. This will only be achieved by extraction of highly pure mucin from diseased bowel. In this regard, post mortem material provides an opportunity for mucin researchers which is not available to workers in other fields because of relative freedom from decomposition. The wedding of mucin technology with immunology is also a major priority. Immunoassay techniques provide the answer to quick and accurate product identification in secretion studies. Specific monoclonal antibodies will provide the route to structural differentiation of antigens in complex mixtures. It is also evident that we must seek to develop a variety of controllable models for the study of functional parameters of mucus in physiological conditions, parasite rejection, neoplasia and inflammatory states. Promising initiatives have been touched upon in this review, but these must only be the beginning. One must conclude, however, by recognizing that advances in knowledge have been truly remarkable since the last conference in 1976. One senses that some of the keys which will one day unlock the gates of this "ill-defined" kingdom are already in hand, while the remainder are at least within reach.

Adenocarcinoma↗

Legionnaires' disease in Durban. A case report.

An isolated case of Legionnaires' disease occurring in Durban is described. The patient presented with bilateral extensive pneumonia. Diagnosis was made by the indirect immunofluorescent antibody test, which showed a fourfold rise in titre from 1 : 128 to 1 : 512. Awareness of the fact that Legionnaires' disease occurs here should result in early recognition and appropriate management of this disease.

Diagnosis, Differential↗

Measles, histocompatibility leukocyte antigen polymorphism, and natural selection in humans.

Profound lymphocytopenia (greater than 2,000 lymphocytes/mm3) occurring within two days of rash in 69 South African black children with measles predicted either death or progression to chronic lung disease in 51 (77%) of 66 children who were followed for at least six weeks. Lymphocytopenia was significantly associated with the presence of histocompatibility leukocyte antigen (HLA) AW32 (P = 0.01), with a relative risk of 5.5. There was a trend toward an association between the presence of particular antigens in the HLA complex and the various indices of humoral and cellular immunity studied. These findings are discussed in terms of variation in the clinical spectrum of the disease and in relation to the evolution of HLA polymorphism.

Antibodies, Viral↗

Immunization against measles in children at risk for severe disease.

Live measles vaccine induced protective levels of antibody in 70% of children with protein-calorie-malnutrition (PCM) within 21 days and possibly in 90% by 42 days. The development of specific antibody was delayed and symptoms due to the vaccine more frequent (64%) in these children than in healthy children. Administration of measles vaccine may have predisposed to an associated fatal pneumonia in one malnourished child. Human measles hyperimmune globulin can maintain adequate antibody levels in most children with PCM (75%) for at least three to four weeks. Vaccination induced protective levels of measles antibody in 83% of healthy children under 10 months of age, which compared well with 86% of successful immunizations done at 10 months or later. There was wastage of vaccine in 40 to 70% of children who, despite a negative history of measles, had protective levels of antibody when admitted to the study. It is suggested that malnourished children in the community or the very young can be safely and effectively vaccinated against measles. But passive immunization is preferred in children with PCM severe enough to be admitted to hospital and thereby at increased risk of exposure to measles and other infections.

Antibodies, Viral↗

Immunological events in acute measles influencing outcome.

77% of 30 children with measles who had severe lymphopenia (less than 2000/mm3; less than 2.0 x 10(9)/1) within 2 days of appearance of rash (group A) subsequently died or progressed to chronic chest disease. This was significantly worse than the outcome in 30 children with measles who had lymphocyte counts more than 2000/mm3 (more than 2.0 x 10(9)/1) (group B) of whom 67% recovered. In group A children the persistence of severe lymphopenia (caused by a reduction in T- and B-cells) for at least 15 days after onset of rash, remained a good predictive index of morbidity and mortality. Reversal of immunoparesis in group A was slower and incomplete 42 days from appearance of the rash in those who subsequently died or developed chronic chest disease compared with those who recovered. All patients who died failed to produce adequate measles antibodies. The therapeutic implications and immunopathological significance of these findings for chronic complications after acute measles are discussed.

Acute Disease↗

Alterations in immune responsiveness in acute measles and chronic post-measles chest disease.

Immune responses in 24 children with acute measles (AM) were compared with those in 20 children who had chronic pulmonary complications (CPMC) following measles. The immuno-suppressive effects of acute measles were extensive: total white cells were reduced and this reduction was accounted for entirely by lymphopenia which was equally expressed among the major lymphocyte sub-populations studied; the function of 'T' cells, assessed by radio-isotope incorporation into phytohaemagglutin (PHA) transformed lymphocytes and delayed skin hypersensitivity (DHR) to dinitrochlorobenzene (DNCB), was depressed. Serum IgA was reduced in AM patients. In contrast there was a relative sparing of the measured indices of immunity in patients with chronic post-measles chest disease, with the major defect being an impaired DHR to DNCB. There were minor alterations of complement components in both groups of patients.

Acute Disease↗

Cell-mediated immunity in measles using the leucocyte migration test.

The cell-mediated immune response was investigated in 21 children with acute measles and in 8 healthy children using the intradermal Heaf and leucocyte migration tests. Tuberculin and purified protein derivative were used as antigens. Whereas all the children with measles were anergic in the in vivo test, two groups of children, i.e. 'reactors' and 'non-reactors' could be delinerated with the in vitro test. The mechanisms responsible for the anergy are discussed.

Child↗