Showing papers on "Cystic fibrosis published in 1979"

Multiple Isolates of Pseudomonas aeruginosa with Differing Antimicrobial Susceptibility Patterns from Patients with Cystic Fibrosis

Abstract: Clinical isolates of Pseudomonas aeruginosa from patients with cystic fibrosis were studied in an effort to determine the unique characteristics of the infecting strains and to elucidate the pattern of colonization. Of 413 patients studied, 81% were chronically infected with P. aeruginosa. Patients from whom P. aeruginosa was never or only occasionally isolated were in better clinical condition than the chronically infected patients. Isolates were classified into six morphologic varieties: classic, rough, mucoid, gelatinous, dwarf, and enterobacter. Most patients had two or more of these varieties. Such multiple varieties from the same individual were of the same serotype but often differed in antibiotic susceptibility as determined by both the disk and the minimal inhibitory concentration methods. These differences were apparent when mucoid strains were compared with nonmucoid strains and when nonmucoid strains were compared with one another. Studies of antibiotic susceptibility should be performed on each morphologically different type of P. aeruginosa obtained from patients with cystic fibrosis. Chronic pulmonary infection is responsible for most of the morbidity and almost all of the mortality in patients with cystic fibrosis. Severe chron

Quantitative evaluation of the development of the exocrine pancreas in cystic fibrosis and control infants.

Abstract: The development of the exocrine pancreas has been determined quantitatively in 31 infants with cystic fibrosis (CF) both with and without meconium ileus and in 29 control infants. In the normal pancreas, the ratio of acinar to connective tissue volume is 0.5 at 32 weeks postconceptional age (PCA) and increases linearly to 2.0 at 52 weeks PGA. In cystic fibrosis infants, with or without meconium ileus, the ration is 0.5 at 35 weeks PCA anddecreases linearly to 0.3 at 52 weeks PCA. The volume of acinar and duct lumens is greater in CF than control infants but is independent of age or acinar volume. The development of the exocrine pancreas in infants with CF with and without meconium ileus diverges from the normal pattern: There is consistent lack of exocrine tissue before or a full-term birth, which persists throghout the age range of this study. CF infants above 42 weeks PCA can be discriminated from controls on the basis of the quantitative assessment of acinar volume.

Inhibitory effect of cystic fibrosis serum on pseudomonas phagocytosis by rabbit and human alveolar macrophages.

Abstract: Summary: This report presents experimental observations indicating the presence of an inhibitory activity in cystic fibrosis (CF) serum which impairs phagocytosis of Pseudomonas aeruginosa by rabbit as well as human alveolar macrophages. Of the 49 patient serum samples studied, 40 consistently showed ≥ 60% inhibition, 3 showed no inhibition and 6 were in the range of 20–60% inhibition of Pseudomonas phagocytosis. In parallel studies, the phagocytosis of S. aureus and S. marcescens was found not to be inhibited by CF serum. Mixing of CF serum with normal serum could not overcome the inhibitory effect, indicating the presence of an inhibitory factor rather than the lack of a necessary component. The inhibitory activity is not lost upon exposure of serum to glass, upon freezing the serum once, or upon heating at 56 C for 30 minutes. Speculation: The serum of cystic fibrosis patients selectively inhibits alveolar macrophage function in vitro; the expression of this inhibitory activity in vivo may compromise effective host control of infection. Investigation of the origin, nature and pathophysiologic role of the activity may suggest new approaches to the control of Pseudomonas pulmonary infection. Pultionary infection is a major factor in the morbidity and mortality associated with cystic fibrosis (CF) (6). Pseudomonas, a uhrquitous organism in the environment, is cystic fibrosis (CF) (6). Pseudomonas, a uhrquitous organism in the environment, is usually not pathogenic for healthy individuals. However, individuals with the chronic lung disease of CF are particularly susceptible to opportunistic Pseudomonas aeruginosa infections. The frequency of this organism in CF pulmonary infections is inadequately explained. It is well known that most CF patients have elevated levels of Pseudomonas antibodies in their sera and pulmonary secretions (l2,14). While recently there has been an indication that a lymphocyte unresponsiveness to Pseudomonas may be acquired as the infection progresses (18,19), no other immunologic abnormality has been consistendy observed (5.10). Extrapulmonary infection is extremely rare and sepsis is almost never, seen after the first months of life (22). This unusual susceptibility to Pseudomonas despite apparently normal systemic humoral and cellular immunity. suggests that local pulmonary host defense mechanisms are defective in CF. Several recent studies have indicated that lung defenses can, to a certain extent, function independently of systemic humoral and cell mediated immune systems (9,15,20,21). Lung defenses include mucociliary transport as well as phagocytic cells, lymphocytes, and immunoglobulin secretion. Since mucociliary transport in some CF patients is compromised (5). clearing of the bacteria becomes more dependent on the efficient action of the phagocytic cells. Previous studies in our laboratory (2) and by Biggar, et al. (I) have shown that CF serum impairs phagocytosis of Pseudomonas by rabbit alveolar macrophages. This report presents experimental observations indicating the presence of an inhibitory activity in CF serum which impairs phagocytosis of Pseudomonas by human as well as rabbit alveolar macrophages.

Hypoelectrolytemia and metabolic alkalosis in infants with cystic fibrosis.

Abstract: The records of all children in the Tucson area diagnosed as having cystic fibrosis (CF) before the age of 12 months were reviewed to ascertain the prevalence of metabolic alkalosis as a major presenting manifestation of CF Five of eleven infants (46%) in whom CF had been diagnosed between 1 and 12 months of age initially were seen with hypokalemia, hypochloremia, and metabolic alkalosis unassociated with marked dehydration, hyperpyrexia, or major pulmonary and/or gastrointestinal symptoms Two infants had repeated episodes of metabolic alkalosis; for one of these infants, both episodes of metabolic alkalosis occurred before the diagnosis of CF It is postulated that chronic loss of sweat electrolytes together with mild gastrointestinal or respiratory illness may predispose the infant with cystic fibrosis to a severe electrolyte and acid-base disturbance The lack of shock and hyperpvrexia together with the apparent chronicity of electrolyte losses differentiates metabolic alkalosis from the heat prostration syndrome, a more acute complication of cystic fibrosis Quantitative sweat testing should be part of the evaluation of any infant with unexplained metabolic alkalosis Serum electrolytes should be assessed regularly in infants with cystic fibrosis during hot weather months

Premature senescence in cultured skin fibroblasts from subjects with cystic fibrosis

Abstract: Cultured skin fibroblasts from subjects with cystic fibrosis exhibited normal population doubling times in early passages. After about 13 cumulative population doublings, cystic fibrosis lines doubled more slowly than controls and ceased doubling after about 19 weekly passages. Control lines continued doubling for 27 passages. The premature senescence noted in cells from subjects with cystic fibrosis reconciles controversial observations of cell doubling reported in the literature. Data presented here demonstrate that experiments with cystic fibrosis cells in late passage may generate misleading results since differences from control lines may be ascribed to generalized senile changes rather than to specific results of the cystic fibrosis genotype.

Defective cellular immunity to Gram-negative bacteria in cystic fibrosis patients.

Abstract: In vitro lymphocyte responses to Pseudomonas aeruginosa have been found to be impaired in cystic fibrosis patients with advanced clinical disease. The responses to Klebsiella pneumoniae, Serratia marcescens, and Proteus mirabilis were studied in a similar group of cystic fibrosis patients and normal individuals. Cystic fibrosis patients found to be unresponsive to pseudomonas were also unresponsive to klebsiella, serratia, and proteus. Responsiveness to Staphylococcus aureus was not impaired in cystic fibrosis patients. We postulate that in vitro lymphocyte responses to several gram-negative bacteria require the function of a lymphocyte subpopulation which may be impaired in some cystic fibrosis patients.

Multifocal myocardial necrosis and fibrosis in pancreatic diseases of children.

Abstract: From a review of 2,000 autopsies of children, 16 cases of extensive necrosis and scarring fibrosis of the myocardium were found. These lesions involved mainly the left ventricle and spared the endocardium, the pericardium, and the coronary vessels. These necrotic of fibrotic heart lesions were found to be closely associated with various pancreatic diseases: cystic fibrosis (11 cases), pancreatic lipomatosis (2 cases), extensive small bowel resection (3 cases, 2 of which were associated with acute interstitial pancreatitis). To explain these unexpected associations, two hypotheses can be put forth: (1) The lack of absorption of some presently undetermined substances indispensable for the correct trophicity of the myocardium, and (2) the release in the blood of proteolytic enzymes with consecutive activation of phlogistic substances such as kinins.

Study of the oligosaccharide units from mucus glycoproteins of meconium from normal infants and from cases of cystic fibrosis with meconium ileus.

Abstract: 1. The mucus glycoproteins in meconium from normal infants and from infants having cystic fibrosis with meconium ileus have been studied. 2. Whereas normal meconium contained about 50% protein-bound carbohydrate, the meconium from cystic fibrosis contained only about 10%. 3. Glycopolypeptides were prepared from the mucus glycoproteins. The oligosaccharide units from this material were released and fractionated. The fractions ranged widely in size and composition. 4. The fractions from cystic fibrosis specimens had a significantly higher content of fucose than those from normal specimens.

Activated complement in the sputum from patients with cystic fibrosis.

Abstract: 14 cystic fibrosis (CF) patients chronically infected with mucoid P aeruginosa and presenting multiple precipitins in serum against this bacterium (CF + P) and 13 CF patients without P aeruginosa infection (CF-P) had their plasma and sputum sol phase examined for albumin, Clq C3/C3c, C4 and C5 by means of electroimmunoassays Their sputum sol phase was examined also for factor B by rocketimmunoelectrophoresis C3c was demonstrated in the sputum sol phase but significantly more frequent (p less than 001) among the CF + P patients than among the CF-P patients Factor B was also demonstrated in the sputum sol phase, but no significant difference in frequency could be demonstrated between the CF + P and the CF-P patients None of the results indicated that a local pulmonary production of complement factors took place Complement activation was significantly (p less than 001) associated with inflammation expressed as increased (formula: see text) The results show the importance of complement mediated inflammation in the pathogenesis of pulmonary tissue damage in patients with CF and support the concept of chronic P aeruginosa lung infection as an immune complex disease in CF patients

Pharmacokinetics of azlocillin in children with cystic fibrosis.

Abstract: 6-E1(R)-2-(oxo-imidazolidine-1-carboxamido)-2-phenyl-acetamido]-penicillanic acid sodium salt (azlocillin, Securopen) was given in doses of 100 and 200 mg/kg body weight to children with cystic fibrosis. After intravenous bolus infections, the serum half-life was 0.82 +/- 0.12 h after the lower dose and 0.98 +/- 0.18 h after the higher dose. This was consequent to a dose limited elimination kinetics due to limitation in both renal and non-renal processes of elimination. Upon doubling of the dose from 100 to 200 mg/kg, the total body clearance dropped from 13.93 to 5.10 1/h. Evaluation of data presented in other publications indicate that a dose limited elimination kinetics is the normal situation for azlocillin. Besides, the serum concentrations of patients with cystic fibrosis were considerably lower than seen in the healthy state. The reason is faster elimination by the renal route in cystic fibrosis.

Laser light-scattering spectroscopy: preliminary results on bioassay of cystic fibrosis factor(s).

Abstract: Summary: The effect of 7 cystic fibrosis sera and 4 normal sera was investigated in 37 cultures of ciliated epithelium of the rabbit trachea. Serum was introduced in the Rose culture chambers in a concentration of 10% by volume. The frequency of ciliary beat was monitored by laser light-scattering spectroscopy. The results show that the response of cilia to sera can be well characterized by laser light scattering. Our preliminary evidence suggests that an early increase in the frequency of ciliary beat, followed by rapid arrest of ciliary activity, is a sensitive and characteristic response produced by cystic fibrosis serum, and not by normal serum. Speculation: The present work was aimed at demonstrating the feasibility of implementing an objective and quantifiable bioassay for cystic fibrosis factor(s). Laser light-scattering spectroscopy is applicable to detection and quantification of ciliary activity. The method may lead to improved bioassays for cystic fibrosis factor(s).

Immunoreactive serum trypsin in diseases of the pancreas.

Abstract: Immunoreactive serum trypsin was measured with a double antibody radioimmunoassay in normal subjects and patients with various diseases of the pancreas. The normal range is 115-350 ng/ml with a geometric mean of 212 ng/ml. No trypsin was found in serum after total duodenopancreatectomy, in about 75% of patients with cystic fibrosis and in a few patients with pancreas carcinoma or chronic pancreatitis. Reduced serum trypsin levels between 10 and 100 ng/ml were measured in the remaining 25% of cystic fibrosis and in one third of the patients with chronic pancreatitis. Serum trypsin was increased to 700-17,000 ng/ml in all patients with acute pancreatitis or during the acute phase of chronic pancreatitis. Absent or reduced serum trypsin is a reliable indicator of total or partial exocrine pancreatic insufficiency whereas considerably increased serum trypsin concentration do indicate acute pancreatitis.

Protease deficiency in plasma of patients with cystic fibrosis. Reduced reaction of 4-methylumbelliferylguanidinobenzoate with plasma of patients with cystic fibrosis.

Abstract: Protease activity in plasma is assayed using 4-methylumbelliferylguanidinobenzoate. The assay is modified by carrying out the reaction in the presence and absence of benzamidine, a competitive inhibitor of trypsin-like proteases. The parameters of the assay are described in detail. Using this assay, our earlier demonstration of a deficiency of protease activity in plasma of patients with cystic fibrosis is confirmed. The activity, corrected for the nonspecific hydrolysis of 4-methylumbelliferylguanidinobenzoate by benzamidine, is expressed as nanomoles of 4-methylumbelliferone released per milliliter plasma. Under standard conditions, the activity in plasma activated with chloroform-ellagic acid was 127.2 +/- 23.1 in 7 controls, 70.4 +/- 11.7 in 11 obligate heterozygotes, and 48.7 +/- 16.6 in 12 patients with cystic fibrosis. Identical results were obtained when unactivated plasma was used. These data demonstrate that the judicious use of specific inhibitors such as benzamidine might be useful in assaying low levels of protease activity in crude systems.