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Biomedical subjects

D W Beatty

Publications and source records attributed to D W Beatty.

At least 19 recordsLinked to original sources

Treatment of chronic granulomatous disease with recombinant gamma interferon.

Chronic granulomatous disease is a rare, primary immunodeficiency associated with serious bacterial and fungal infections caused by phagocytic defects of oxidative metabolism. To date the mainstay of management has been aggressive treatment of infections and the use of prophylactic antibiotics. Two patients, who showed remarkable clinical improvement when treated with recombinant gamma interferon, are reported. Both have been on treatment for at least 18 months and have continued to thrive and remain free of infections.

Child, Preschool

IgG subclass values from normal children in Cape Town.

Sensitive and reproducible enzyme-linked immunoabsorbent assays (ELISA) have been developed to quantitate IgG subclass levels using monoclonal antibodies. Normal values for serum IgG subclass levels were determined in 300 healthy children between 6 months and 14 years of age and in 80 adults. High levels of IgG1 and delayed maturational development of IgG2 in children from Cape Town are different to results reported from developed countries. Genetic differences may account for this.

Adolescent

Iron fortification of infant milk formula: the effect on iron status and immune function.

We conducted a randomized double-blind trial of a cow's milk infant formula with increased iron fortification in order to confirm its safety and to measure its effects on iron status and immune function. A group of full-term, well nourished and healthy infants was followed from the age of 3 months to 1 year. A control group of 74 infants was given a commercially available infant formula containing 8.3 mg Fe/100g. The test group of 75 infants received a similar formula with 40 mg Fe/100 g. The formula with the extra iron proved to be safe and, when compared with the control group, the children in the test group had significantly improved iron status as reflected by the proportion of children classed as normal (25 of 61 cf. 44 of 65; p less than 0.003), and by the mean values of the haemoglobin concentration (11.5 cf. 11.9 g/dl; p = 0.04), red cell distribution width (15.5% cf. 14.4%; p = 0.0005), red cell zinc protoporphyrin (3.4 cf. 4.0 micrograms/g Hb; p = 0.04) and ferritin (29 cf. 17.3 micrograms/l; p = 0.004). The extra iron fortification depressed zinc concentration in plasma (90.6 cf. 83.5 micrograms/l; p = 0.05). There was no significant difference between the two groups for laboratory measures of immune function or for incidence of infection. No adverse effects such as infection could be attributed to the increased iron. We conclude that iron fortification of cow's milk infant formula may be safely increased to 40 mg/100 g (i.e. by a factor of 4.8 over the common concentration of 8.3 mg/100 g), but that this has less than the expected effect on iron status. Further studies are required to define (a) the long-term role of facilitators of iron absorption such as ascorbic acid, (b) the interaction of iron with absorption of divalent trace elements such as zinc, and (c) the effect of iron status on immune function and susceptibility to infection.

Anemia, Hypochromic

IgM rheumatoid factor in congenital syphilis: associations with clinical and laboratory findings.

IgM rheumatoid factor (RF), measured by means of an ELISA, was detected in 92% of infants with congenital syphilis. Elevated levels were found to correlate with liver and renal involvement as well as the extent of the disease (P less than 0.05). In addition, levels of circulating immune complexes were closely related to the RF concentration (P less than 0.001). Following treatment of the infants both RF levels and VDRL titres declined at a similar rate (P less than 0.001). These findings indicated a close relationship between the disease process and IgM RF levels. It is postulated that IgM RF may add to immune complex deposition and exacerbate tissue damage in congenital syphilis.

Antigen-Antibody Complex

Hyper IgM with combined immunodeficiency.

This report describes a fourteen year old girl with an unusual immunodeficiency characterized by persistent lymphadenopathy and associated with hypogammaglobulinaemia, excessive IgM production and a severe T cell defect. Total T cell and T helper cell numbers were reduced and T cell proliferative responses to mitogens were poor. Serum IgM levels showed marked fluctuations and peaks correlated with acute tender lymphadenopathy. She was treated with intravenous gammaglobulin and prophylactic antibiotics. Although defective isotype switching of B cells into IgA and IgG producing cells has been accepted as the mechanism of the hyper IgM syndrome, it is becoming increasingly evident that T cell function is not uncommonly involved and may be responsible for impaired isotype switching.

Adolescent

Human monoclonal antibodies: analysis of two antibodies derived from lymphocytes of a patient with acute rheumatic fever.

Human monoclonal antibodies were produced by fusion of peripheral blood lymphocytes from a patient with acute rheumatic fever, with the HGPRT-non-secreting murine (Balb-c) cell line SP2/0Ag14. Heterohybridomas were selected by screening against rheumatic fever-associated group A streptococci using an ELISA, and against paraffin wax-embedded human heart sections using an immunoperoxidase technique. Two human IgM monoclonal antibodies were selected for further analysis by Western blotting and ELISA. Both antibodies demonstrated multispecificity by immunoblotting and ELISA. One of the monoclonals bound to 48 kD and 83 kD bands common to group A streptococcal and heart antigen preparations. Both human monoclonal antibodies bound to a 43 kD constituent band common to human heart and sarcolemma membrane extract. Inhibition studies performed using a competitive solid phase immunoassay confirmed shared epitopes between group A streptococci and human heart. The significance of these monoclonal antibodies to the pathogenesis of rheumatic fever is uncertain.

Acute Disease

Childhood near-drowning--factors associated with poor outcome.

Anoxic cerebral damage is the limiting factor in recovery from near-drowning accidents. This study reports factors associated with poor outcome in 100 near-drowned patients admitted to the Red Cross War Memorial Children's Hospital from 1976 to 1987. The study was designed as a retrospective folder search. Children with fixed dilated pupils, flaccidity, decerebrate or decorticate posturing, or clinical signs of cerebral oedema are more likely to have a poor outcome. Patients with metabolic acidaemia and those requiring cardiopulmonary resuscitation in the emergency room or subsequent mechanical ventilation also do poorly. Those requiring more aggressive management can be identified and a more accurate working prognosis may be possible in the hours after the accident.

Adolescent

Immune studies in infants with congenital syphilis.

Seventeen neonates with congenital syphilis were studied to determine the immune response of the fetus following intra-uterine infection with Treponema pallidum. The results were compared with those from healthy controls matched for gestational age, birth weight and sex. B cells, IgM, and circulating immune complexes were significantly elevated in the infected newborns. There were no differences in lymphocyte transformation to phytohaemagglutinin (PHA) and in the CD3, CD4, and CD8 lymphocytes between infants with congenital syphilis and controls. Newborns with congenital syphilis have a heightened humoral response but no quantitative abnormality in cell-mediated immunity. Speculation on the role of the circulating immune complexes is presented.

Antigen-Antibody Complex

X-linked agammaglobulinaemia.

X-linked agammaglobulinaemia (XLA) is a rare immunodeficiency disorder affecting only male subjects. There is an absence of all serum immunoglobulins and circulating B cells. T-cell function and numbers are normal. The clinical characteristics are recurrent pyogenic infections starting in infancy, hypoplasia of lymphoid tissue and a family history in about half the cases. Ten patients with XLA have been seen over the last 14 years at Red Cross War Memorial Children's Hospital, Cape Town. Chronic infections causing significant morbidity occurred in half our patients and 2 have died. Intravenous of gammaglobulin replacement therapy is superior to the intramuscular form. The recommended dose is 200-400 mg/kg/mo., although the optimal dose and frequency of the gammaglobulin infusion should be individualised for each patient.

Agammaglobulinemia

Group B meningococcal infection in children during an epidemic in Cape Town, South Africa.

One hundred and thirteen children with meningococcal infection were studied during an epidemic caused by N. meningitidis group B. Fifteen per cent presented with only meningeal symptoms, the remainder showed signs of septicaemia or combined septicaemia and meningitis. Sixteen per cent of the children were in shock and 18% required admission to the Intensive Care Unit (ICU). The mortality was 4.4%. More than half the children were younger than 2 years old. There was no statistical association between the age or nutritional state of the children and any of our measures of severity. A short history of symptoms was more common in children who presented with septicaemia and severe illness, who needed admission to the ICU, or who died. Diagnosis was confirmed by routine bacteriological methods and counter-immuno-electrophoresis (CIE) in 104 children. Eighty-six per cent of the isolates were group B type 2. A history of recent antibiotic treatment was associated with fewer positive cultures, but detection of meningococcal antigen by CIE was not affected by this. CIE antigen detection was not reliable because of the high incidence of false-negative results.

Blood

Ataxia-telangiectasia. X,14 translocation, progressive deterioration of lymphocyte numbers and function, and abnormal in vitro immunoglobulin production.

Three children with ataxia-telangiectasia have been followed up since their early childhood. Sequential immunological, biochemical and chromosome studies have been performed over the last 7 years. All the children showed progressive cerebellar ataxia and inexorable neurological deterioration. Further evidence for the progressive nature of this condition is the fall in lymphocyte counts, deterioration of lymphocyte transformation responses to mitogens, and an increase in chromosomal translocations and breakage. Elevated serum alpha-fetoprotein levels are a highly characteristic and useful diagnostic finding in this condition. Two of the patients had an X,14 translocation. In vitro studies of immunoglobulin synthesis suggest an intrinsic defect in B-cell synthesis as well as decreased helper T-cell activity. In spite of moderately severe and progressive abnormalities in the immune system, sinopulmonary infections have not been prominent in our patients.

Adolescent

Lymphatic abnormalities in Noonan syndrome: A case report.

Lymphatic abnormalities are not generally recognized as part of the Noonan syndrome. A child with this condition in whom unique and widespread lymphatic abnormalities were demonstrated by lymphography is described. Both T and B lymphocytes were detected in chylous fluid drained from the thorax. In addition, the child was found to have a protein-losing enteropathy and cardiovascular defects. The clinical spectrum of the Noonan syndrome may include animalies of the lymphatic system.

Cardiac Catheterization

Deficiency in kwashiorkor serum of factors required for optimal lymphocyte transformation in vitro.

Blastogenic responses of normal human peripheral blood lymphocytes cultured in media supplemented with serum from children with kwashiorkor were, on average, 47.7% of those observed when the same cells were cultured in the presence of normal AB serum. Incorporation of radioactive uridine was also diminished in the presence of normal AB serum. Incorporation of radioactive uridine was also diminished in the presence of kwashiorkor serum indicating that lectin-induced RNA synthesis was also affected. The kwashiorkor serum effect was not due to a cytotoxic action nor could it be attributed to the presence of saccharides or other inhibitors of the inducing lectins. Mixing experiments showed that kwashiorkor serum was not inhibitory, but that it lacked factors present in normal serum that are required for optimal lymphocyte blastogenesis. The deficiency of these factors could largely be rectified by supplementing kwashiorkor serum with an ultrafiltrate of normal serum containing components with molecular weights of less than 500 Daltons. We conclude that nutritional deprivation of severity sufficient to cause kwashiorkor leads to a deficiency of low molecular weight lymphocyte growth factors. This lack may contribute to the immunodeficiency associated with the disease.

Cell Survival

Cellular immune function in marasmic and underweight infants with prolonged diarrhoea.

Lymphocytes from 10 marasmic and underweight infants with prolonged diarrhoea responded normally to phytohaemagglutinin stimulation. There was no gross deficiency in the total number of lymphocytes, serum immunoglobulins, or serum C3. Defective cellular immunity does not appear to play a major role in the pathogenesis of diarrhoea in these children.

Blood Proteins

Levamisole.

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Autoimmune Diseases

The effects of kwashiorkor serum on lymphocyte transformation in vitro.

The serum from twelve children with kwashiorkor was deficient in its ability to support lymphocyte transformation in vitro, whereas lymphocytes from these children responded to phytohaemagglutinin and al-ogeneic lymphocytes in a relatively normal manner when cultured in normal serum. This serum abnormality improved with therapy and could not be clearly correlated with the degree of malnutrition, the presence or absence of infection or other laboratory manifestations of kwashiorkor. These observations indicate that defective cellular immune reactions in kwashiorkor may be symptomatic of a lack of some humoral factor and do not necessarily reflect an intrinsic cellular defect.

Blood Proteins