Hemophilia in the 1990s: principles of management and improved access to care.
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Blood Transfusion↗
Biomedical subjects
K A Rickard
Publications and source records attributed to K A Rickard.
Progression of HIV-related disease is associated with HLA DQ and DR alleles defined by restriction fragment length polymorphisms.
A cohort of 139 hemophiliacs was typed for HLA D region genes by means of restriction fragment length polymorphisms (RFLPs) detected by HLA DQ and DR gene probes. Disease progression was studied in the 65 HIV antibody-positive patients, who were infected by contaminated clotting factor before 1985. Strong associations were found between disease progression in HIV-infected patients and allelic DNA fragments revealed by a DQ alpha cDNA probe. A 5.5 kb fragment was reduced in frequency and a 4.6 kb fragment increased in frequency (p less than 0.005) in the faster progressing group, as measured both by development of CDC Category IV clinical symptoms and CD4 number less than 200 x 10(6)/l. These results correlate with DR types deduced from the RFLP patterns revealed by DR beta and DQ alpha gene probes. A decrease in DR4 and an increase in both DR5 and the DR3 subtype found in the A1 B8 DR3 haplotype were associated with disease progression (p less than 0.05).
Alleles↗
Observations of development of resistance to detachment of cultured bovine bronchial epithelial cells in response to protease treatment.
Protease injury of the bronchial epithelium may play an important role in the pathogenesis of many airway diseases including asthma and chronic bronchitis. We hypothesized that neutrophil elastase can cause significant injury to the bronchial epithelium leading to detachment of bronchial epithelial cells. This detachment might be prevented if elastase is released into the airway lumen and the bronchial epithelium forms a barrier preventing access to the basal attachment sites. To assess this, the detachment of bronchial epithelial cells by elastase from extracellular matrix was measured. An increase in the resistance to detachment with time in culture was observed. The resistance to detachment was confirmed in bronchial epithelial cells, which were grown to electrically resistant monolayers on millipore filters and exposed to trypsin and elastase applied to both the apical and basal surfaces. Significantly greater detachment occurred when the proteases were applied at the basal surface versus the apical surface. Injury to the bronchial epithelium may enhance the proteolytic effect on the epithelium by disrupting epithelial barrier function. This was tested by exposing bronchial epithelial cell cultures to cigarette smoke extract before exposure to trypsin and elastase. The detachment of the bronchial epithelial cells exposed on the apical surface was increased greatly after smoke exposure. These data suggest that an intact bronchial epithelium can act as a barrier against proteolytic injury. Such a mechanism might protect the airway epithelium during intraluminal inflammation, and, if defective, might potentiate cigarette smoke-induced airway injury.
Animals↗
Modulation of neutrophil and mononuclear cell adherence to bronchial epithelial cells.
Neutrophils and mononuclear cells have been associated with the lower respiratory tract inflammation observed in both acute and chronic bronchitis. In order to transit into and remain within the airways, neutrophils and mononuclear cells would likely need to adhere to bronchial epithelium. To test this hypothesis, bovine bronchial epithelial cells (BBECs) were isolated and cultured on a round coverslip. After 7 to 10 days, 51Cr-labeled neutrophils and mononuclear cells were evaluated for their capacity to adhere to the BBEC monolayer. Both neutrophils and mononuclear cells readily bound to the BBEC monolayer (10.8 +/- 1.2% bound neutrophils; 40.5 +/- 2.8% bound mononuclear cells). Stimulation of the neutrophils and mononuclear cells with phorbol 12-myristate 13-acetate (PMA) increased the adherence (45.8 +/- 10.6% bound neutrophils, P less than 0.01 compared with unstimulated cells; 58.7 +/- 6.2% bound mononuclear cells, P less than 0.01 compared with unstimulated cells). Importantly, stimulating the BBEC monolayer with PMA, bacterial lipopolysaccharide, or a cigarette smoke extract for 4 to 72 h also increased the adherence of both cell types (P less than 0.01, all comparisons at 24 h). The adherence was not decreased by exposure of either the BBEC monolayer, the neutrophils, or the mononuclear cells to cycloheximide or to the anti-CD11/CD18 monoclonal antibody 60.3 (P greater than 0.05). However, exposure of the BBEC monolayer to trypsin before addition of the neutrophils significantly decreased adherence (P less than 0.05). Because neutrophils and mononuclear cells are thought to mediate cell cytotoxicity by adhering to the target cells, BBECs were labeled with 51Cr, and 51Cr release was measured as an index of cytotoxicity. There was a modest increase in 51Cr release by the addition of unstimulated neutrophils and mononuclear cells, and culturing the BBEC monolayer with PMA before the addition of the neutrophils or mononuclear cells resulted in a further modest enhancement of 51Cr release (P less than 0.05). Similar results were obtained using lactate dehydrogenase release as a measure of cytotoxicity. These results demonstrate that inflammatory cells can adhere to BBECs and may be capable of mediating cytotoxicity and adherence and cytotoxicity can be increased by stimulating BBECs.
Animals↗
Extracellular matrix and bronchial epithelial cell migration.
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Animals↗
Haemophilia in the 1990s: report of a joint meeting of the World Health Organization and World Federation of Hemophilia.
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Blood Transfusion↗
Attachment characteristics of bovine bronchial epithelial cells to extracellular matrix components.
Attachment of cells to extracellular matrix (ECM) plays an important role in the regulation of cell growth and differentiated function. We hypothesized that bronchial epithelial cells preferentially attach to ECM proteins and utilize specific receptors for ECM proteins. Bronchial epithelial cells were obtained from bovine lung by protease digestion. Both freshly isolated and cultured bronchial epithelial cells were plated onto plastic petri dishes coated with bovine serum albumin, type I collagen, type IV collagen, fibronectin, laminin, ECM synthesized by cultured bronchial epithelial cells, or uncoated. Freshly isolated cells demonstrated significant attachment to ECM but weak attachment to other matrix proteins. Cultured bronchial epithelial cells attached well to ECM; however, they had relatively increased attachment to type I collagen, type IV collagen, fibronectin, and laminin compared to freshly isolated cells. To determine whether the attachment of bronchial epithelial cells is arginine-glycine-aspartic acid (RGD)-mediated, an RGD-containing peptide known to block attachment mediated by many integrin receptors was added to the media (400 micrograms/ml). There was no inhibition of attachment of freshly isolated cells; however, there was significant but not complete inhibition of the attachment of the cultured cells to type IV collagen, laminin, and fibronectin, but not to type I collagen or ECM. Thus, freshly isolated bronchial epithelial cells readily adhere to ECM, and the attachment does not appear to be mediated by RGD-dependent receptors. Cultured bronchial epithelial cells demonstrate increased attachment to component proteins of ECM, and this attachment is, in part, to RGD-dependent receptors.
Animals↗
Food and nutrient intake of 6- to 12-month-old infants fed formula or cow milk: a summary of four national surveys.
Food and nutrient intakes of infants during the second 6 months of life were summarized with the use of four national surveys as the data base. Three of the surveys, the second National Health and Nutrition Examination Survey (1976-1980), the Ross Nutrition Survey (1984), and the U.S. Department of Agriculture Nationwide Food Consumption Survey (1977-1978), summarized and compared the nutrient composition of the diets of infants fed formula with that of the diets of infants fed cow milk during the second 6 months of life. The Gerber Nutrition Survey (GNS) summarized the nutrient composition of the diets of infants fed formula, cow milk, or human milk, or a combination of these, during 1986. Iron-fortified formula with beikost provided adequate but not excessive intakes of all nutrients for infants during the second 6 months of life with the possible exception of calcium for older infants. In contrast to cow milk, formula provided readily absorbed and adequate iron, generous linoleic acid, and adequate but not excessive intakes of protein, phosphorus, sodium, and potassium. The distribution of energy between protein, carbohydrate and fat, and potential renal solute load was reasonable in infants fed formula. Cow milk with beikost provided low intakes of readily bioavailable iron and linoleic acid and high intakes of protein, calcium, phosphorus, sodium, potassium, and potential renal solute load during the second 6 months of life. The diets of infants fed low-fat milks were even lower in linoleic acid and higher in volume of food consumed, protein, calcium, phosphorus, sodium, potassium, and potential renal solute load than the diets of infants fed whole cow milk. Apparently, infants fed cow milk were treated differently than those fed formula (i.e., they were given more solids and table foods and less baby food at all ages and less volume of milk at 9 and 12 months of age). These data provided the basis for the development of practical suggestions for feeding infants during the second 6 months of life.
Animals↗
Growth outcome and feeding practices of the very low birth weight infant (less than 1500 grams) within the first year of life.
Growth outcome for 1 year of corrected age and feeding practices during that first year of life were described for a large population of very low birth weight (VLBW) infants. Growth patterns of weight, length, and occipitofrontal circumference through 12 months of corrected age, and weight/length ratios at 12 months, were determined for 122 VLBW infants less than or equal to 1500 gm and less than or equal to 35 weeks of gestational age at birth; feeding practices were surveyed within a subpopulation of 89 infants. Differences in growth were apparent when infants were grouped according to sex and appropriateness of intrauterine growth. When the mean values of each group were compared, the female infants of appropriate size for gestational age demonstrated growth at higher percentiles (National Center for Health Statistics term-infant norms) for all three measurements (weight, length, and occipitofrontal circumference). Male infants whose size was appropriate for gestational age, and male and female infants who were small for gestational age, all grew similarly, at lower percentiles for weight and length, when compared with the same norms. Growth in occipitofrontal circumference was closest to term infant norms in all subgroups of infants. The majority of the infants, regardless of subgroup, achieved weights and lengths greater than 5th percentile and proportionate growth with a normal weight/length ratio. At 12 months of corrected age, 30% remained at less than 5th percentile in weight, 21% in length, and 14% in occipitofrontal circumference. Eighteen infants (15%) had a marked discrepancy in weight for length, with a weight/length ratio less than 5th percentile. Three prevalent practices that could result in compromised nutrition were identified: (1) cereals were introduced at an early age, (2) 2% and skim cow milk were fed to approximately 50% of the infants within the first year of life, and (3) whole cow milk was introduced to some VLBW infants at an early age. Caretakers apparently viewed their infants in terms of chronologic age rather than age corrected for prematurity when it came to the initiation of solids and cow milk. Whether increased attention to appropriate feeding practices during the first year of life would result in a more favorable growth outcome for VLBW infants is not known.
Animals↗
Septic arthritis in human immunodeficiency virus infected haemophiliacs.
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Acquired Immunodeficiency Syndrome↗
Lung fibroblasts produce growth stimulatory activity for bronchial epithelial cells.
Interaction between lung fibroblasts and airway epithelial cells may play an important role in lung morphogenesis and airway repair after injury. Even though many reports have suggested that mesenchymal fibroblasts have a growth stimulatory effect on surrounding epithelial cells, very few have attempted to confirm and characterize the growth stimulatory activity in isolated cell systems. We cultured human fetal lung (HFL-1) fibroblasts, harvested supernatant-conditioned media under serum-free conditions, and examined their growth stimulatory effect on bovine bronchial epithelial cells by a variety of techniques, including direct enumeration, thymidine uptake, and metaphase arrest. We also partially characterized the growth stimulatory activity and examined the effect of an inhibitor of DNA synthesis on its release. The results demonstrate that HLF-1 fibroblasts release growth stimulatory activity for bovine bronchial epithelial cells. This activity is nondialyzable, protease-sensitive, acid-stable, and lipid-inextractable and thus appears to have the property of protein; it may be produced by de novo synthesis. Molecular sieve chromatography on Sephadex G-75 indicates an approximate molecular mass of 6,000 D. This growth stimulatory activity is likely to play roles in lung morphogenesis and airway repair after injury.
Animals↗
Separation of bovine bronchial epithelial cell subpopulations by density centrifugation: a method to isolate ciliated and nonciliated cell fractions.
Bronchial epithelial cells isolated by protease digestion can be cultured in vitro for the study of proliferation and differentiation. However, these cells represent a heterogenous population, the components of which likely interact with one another. We attempted to utilize density gradient centrifugation as a method to prepare subpopulations of these bronchial epithelial cells. The suspension of the cells obtained by protease digestion of the bovine bronchi was mixed with an equal volume of colloidal silica reagent, Sepracell-MN, and centrifuged to form a continuous density gradient. Two distinct cell layers were identified in addition to a cell pellet at the bottom. Cells from fraction A (top layer) were more than 95% ciliated cells by morphologic examination. These ciliated cells were recovered intact as assessed by trypan blue dye exclusion and by watching beating of their cilia. The cells from fraction C (bottom layer) were 89.9 +/- 3.88% nonciliated, small round cells with a densely staining nucleus and scant cytoplasm. Comparison of cell morphology of these cells with basal cells in vivo and electron microscopic examinations suggested that these cells were basal cells. These basal cells showed an exponential cell proliferation until confluence in Ham's F12 with supplements, LHC9, and a 1:1 mixture of Medium-199 and modified Eagle's medium with 2% fetal calf serum. In contrast, the cells from fraction A grew minimally in all conditions tested. This difference was also shown in the study of DNA synthesis by [3H]thymidine uptake. Enzyme-linked immunosorbent assay for release of bovine fibronectin into cultured media indicated that fraction C cells secreted much more fibronectin (532 +/- 5.28 ng/10(6) cells/h) than fraction A cells (73.4 +/- 1.00). We also used Percoll as a density-gradient reagent and showed potential usefulness in the preparation of cell fractions of bronchial epithelial cells. In conclusion, it was possible to separate ciliated and nonciliated, presumably basal, cells of bovine bronchial epithelial cells. These differed in growth and fibronectin secretion. Studies of airway cell biology may be aided by the availability of more homogenous cell populations.
Animals↗
Immunophenotypic analyses of cultured hemopoietic mast cells.
Immunophenotypic analyses of immature stage (day 19-23), intermediate stage (day 28-32), mature stage (day 34-37), and older stage (day 42-44) human hemopoietic mast cells from colonies grown in semi-solid agar cultures were performed to study the ontogeny and identity of this cell type and its relationship to other leukocytes. Intermediate to mature stage mast cells were positive with the YB5.B8 mouse monoclonal antibody, (McAb) specific for human mast cells, whereas the reactivity of immature mast cells with this McAb was inconsistent and older cells were generally negative. Mast cells at all stages of maturation were strongly positive for IgE receptor sites and negative with the Bsp-1 McAb, specific for human basophils. Mast cells at all stages of maturation were also strongly positive with the monocyte McAbs RPA-M1 (CD11), positive with the monocyte McAb OKM5 and the monocyte/granulocyte McAbs BMA-210 and MY7 (CD13), strongly positive with the B-cell markers J5 (CD10) and anti-IgM, and positive with the plasma cell marker PCA-1 and to a lesser extent with the activated B-cell marker CD23. The mast cells were also strongly positive with anti-CD45 to the common leukocyte antigen and positive with an antibody to HLA-DR and an antibody to FVIIIC. They were negative for specific T-cell markers. The diversity of this phenotype supports the current concept that mast cells originate from the pluripotential progenitor cells in the bone marrow.
Antibodies, Monoclonal↗
The impact of HIV on health care delivery in haemophilia.
The impact of HIV infection on health care delivery in haemophilia has been enormous and epoch making. Essential modifications and developments in blood product preparation have led to a shortage of FVIII concentrates and an increased cost to the consumer of the final product. The complexity and extent of the clinical complications in HIV positive haemophiliacs has opened up entirely new medical approaches to haemophilia care. The impact of the antibody positive haemophiliac on his immediate and extended family has been deeply emotional. Health care workers initially developed a negative and hostile approach to the haemophiliac group. This attitude has softened but there has been a drop-out of medical and paramedical staff involved in health care delivery in haemophilia. Finally, because of current viral safety and increased purity of factor VIII and IX concentrates, non infected haemophilic families may look to the future with increased optimism.
Blood Banks↗
Integration of nutrition support into oncologic treatment protocols for high and low nutritional risk children with Wilms' tumor. A prospective randomized study.
Benefits and risks of nutrition support were evaluated in 31 malnourished children with newly diagnosed Wilms' tumor managed according to the third National Wilms' Tumor Study protocol. Patients were classified at diagnosis as being at high nutritional risk (HNR, n = 19) or low nutritional risk (LNR, n = 12). Ten HNR patients were randomized to central parenteral nutrition (CPN) and nine HNR patients were randomized to peripheral parenteral nutrition (PPN) plus enteral nutrition (EN) for 4 weeks of initial intense treatment and EN (nutritional counseling, oral foods and supplements) thereafter. Thirteen HNR patients (seven CPN, six PPN) completed the protocol. Twelve LNR patients received EN; 11 Stage I malnourished patients were randomized to 10 or 26 weeks of chemotherapy. Dietary, anthropometric, and biochemical data were determined for HNR patients at weeks 0-4, 6, 13, 19, and 26 and for LNR patients at weeks 1, 2, 5, and 26. In HNR patients, adequate parenteral nutrition support reversed protein energy malnutrition (PEM), and prevented chemotherapy and radiotherapy delays due to granulocytopenia. CPN was superior to PPN in reversing PEM: energy intake, weight gain, and retinol binding protein were higher (P less than 0.05). LNR patients lost weight and fat reserves in the first 2 weeks of treatment; depletion persisted at week 5, and 25% had chemotherapy delays. Thereafter, EN reversed PEM in patients with both chemotherapy regimens. These data suggest that CPN is preferable during initial intense treatment for HNR patients, and that, although EN is ineffective in preventing depletion and treatment delays in the first 5 weeks of treatment for LNR patients, it is effective thereafter.
Abdomen↗
Effectiveness of two methods of parenteral nutrition support in improving muscle mass of children with neuroblastoma or Wilms' tumor. A randomized study.
The short-term and long-term effectiveness of central parenteral nutrition (CPN) versus peripheral parenteral nutrition (PPN) in improving muscle mass (arm muscle area [AMA]) was evaluated for 24 malnourished children with newly diagnosed Stage IV neuroblastoma (n = 14) or Stages II-V Wilms' tumor (n = 10). Patients were randomized to either CPN or PPN plus enteral nutrition (EN: intense nutrition counseling, oral foods, and supplements) for 4 weeks followed by EN until week 10. Oncologic treatment was similar for each tumor type. Dietary, anthropometric, and biochemical measurements were obtained at weeks 0, 4, and 10. During weeks 1 through 4, energy (CPN: means 100 +/- 4; PPN: means 96 +/- 4% of healthy children) and protein (CPN: means 2.5 +/- 0.1; PPN means 2.7 +/- 0.2 g/kg) intakes of the two groups did not differ. The AMA increased (P less than 0.05) with 4 weeks of CPN but not with PPN; changes thereafter with EN were not significant. Weight (P less than 0.05) and triceps skinfolds (P less than 0.01) increased with 4 weeks of PN in both groups and decreased with EN thereafter (P less than 0.01) but were higher at week 10 than diagnosis. Increases in albumin in both groups reached significance at week 10 (P less than 0.05). These data show that CPN improves AMA in malnourished children with neuroblastoma or Wilms' tumor when energy and protein intakes are adequate. The AMA gains can be maintained thereafter with EN.
Anthropometry↗
Hemophilia: state of the art of hematologic care 1988.
Since 1982, when the World Federation of Hemophilia first published a document on the state of the art of hemophilia diagnosis and care, there have been lights and shadows in this field. Although the widespread infection of hemophiliacs with the human immunodeficiency virus (HIV) contaminating clotting factor concentrates is still a threatening and formidable shadow, the gloomy picture brought about by the AIDS epidemic is partially lightened by spectacular improvements in therapy and diagnosis. Carrier detection and first-trimester prenatal diagnosis can now be performed accurately in most kindreds by analysis of DNA of the factor VIII or IX genes. An important step forward towards the elimination of the risk of blood-borne infections transmitted by plasma products was recently made through the application of virucidal methods to clotting factor concentrates. Since HIV appears more vulnerable to such methods than the hepatitis viruses, currently available concentrates can be considered substantially free from the risk of transmitting HIV infection. Even though transmission of hepatitis is much reduced but not totally abolished, virucidal methods are continuously being improved, so that it can be foreseen that concentrates will become safer and safer. Finally, factor VIII produced by recombinant DNA technology is undergoing the first clinical trials in hemophiliacs. Hopefully, it will free from the risk of transmitting infections and will be available in sufficiently large amounts to meet the need of hemophiliacs worldwide. In 1982, the World Federation of Hemophilia published a message on the status of diagnosis and treatment of hemophilia. Since then, hemophilia care has been complicated by widespread infection of hemophiliacs with human immunodeficiency virus (HIV).(ABSTRACT TRUNCATED AT 250 WORDS)
Hematology↗