Denmark to the rescue.
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Cystic Fibrosis↗
Biomedical subjects
R C Stern
Publications and source records attributed to R C Stern.
Nontuberculous mycobacteria in cystic fibrosis. An autopsy study.
We retrospectively studied lung and hilar lymph nodes at autopsy in 18 patients with cystic fibrosis (CF) who had antemortem sputum cultures positive for nontuberculous mycobacteria (NTM). Histologic features were compared with those of 18 patients with CF who had negative antemortem cultures. The most frequent species isolated was M. chelonae group (10 patients). Multiple cultures were positive for NTM in six patients. Three patients were clinically considered to be infected, and two received antimycobacteria drugs. Necrotizing pulmonary granulomas associated with granulomatous organizing pneumonia were found at autopsy in two patients, each of whom had multiple positive sputum cultures and clinical evidence of infection. In one of these, mycobacterial infection was considered to be an important factor in her terminal illness. Neither necrotizing granulomas nor granulomatous organizing pneumonia were seen in the lung tissue of patients whose antemortem cultures were negative for mycobacteria. There was no difference in the prevalence of other granuloma-like lesions between those with and those without positive sputum cultures. No mycobacteria-related granulomas occurred in hilar lymph nodes, although histoplasma granulomas involved hilar lymph nodes of three patients. We conclude that granulomatous mycobacterial lung disease is present in a minority of patients (two of six patients in this study) who have multiple positive cultures. Histologic evidence of infection was not found in patients who had only one of multiple sputum cultures positive for NTM.
Adult↗
Urolithiasis and cystic fibrosis.
PURPOSE: We determined whether cystic fibrosis patients are at increased risk for the development of urolithiasis. MATERIALS AND METHODS: Telephone interviews were conducted with 201 cystic fibrosis patients older than 15 years to identify those with a history of urolithiasis. Histories were confirmed by chart review, and only patients with urolithiasis documented by excretory urography, renal ultrasound or spontaneous passage of a stone were included. RESULTS: A total of 11 patients (5.5%) had documented urolithiasis, with 2 or more episodes in 7. Mean age at initial episode was 27.0 years (range 19 to 33). CONCLUSIONS: Cystic fibrosis patients may be at increased risk for urolithiasis compared to age-specific prevalence rates for stone disease in the general population.
Adult↗
3849+10 kb C-->T mutation and disease severity in cystic fibrosis.
50% of patients with cystic fibrosis (CF) are homozygous for the delta F508 mutation, but the remainder have at least one of many other less common mutations. The 3849 + 10 kb C-->T splice mutation seems to be associated with less severe disease. We report ten CF patients who are hemizygous for this mutation. Three male patients do not have azoospermia (sperm counts 12, 53, and 198 x 10(6)/mL). Another boy died before CF was diagnosed; his genital tract appeared normal at necropsy. All patients had clinically sufficient exocrine pancreatic function. Pulmonary disease was delayed in onset in most of these patients (range < 1 to 16; median 9 years), but then became severe in some, progressing to death (in two) and need for transplantation in one. Sweat chloride concentration was abnormal (80 mmol/L) in one patient but in others was in the intermediate range (45-65 mmol/L). There was substantial variation in pulmonary disease severity within sibships. These observations suggest some dissociation in genetically determined severity between different organs. There was some evidence among these patients of a tendency for disease of the genital tract to become progressively more severe. Perhaps sperm banking should be offered to male patients. We speculate that some normal CF transmembrane conductance regulator is made in patients with this splice abnormality.
Adolescent↗
Cross-sectional and longitudinal studies of naturally occurring antibodies to Pseudomonas aeruginosa in cystic fibrosis indicate absence of antibody-mediated protection and decline in opsonic quality after infection.
Most patients with cystic fibrosis (CF) develop chronic endobronchial infection with mucoid Pseudomonas aeruginosa. It has been suggested that opsonic antibodies to the mucoid exopolysaccharide of P. aeruginosa protect older CF patients (> 12 years of age) who have remained free of colonization by this organism. Serum antibodies from chronically infected CF patients had greater total complement-dependent opsonic activity than did those of older noncolonized patients (P < .02), but when bound antibody was equalized, opsonic quality was greater for the latter group (P < .03). In longitudinal studies, antibody titers to mucoid P. aeruginosa rose greatly after initial infection, but opsonic quality declined (P = .002). Twenty CF patients who passed age 12 free of P. aeruginosa colonization developed chronic P. aeruginosa lung infection at ages 14-35 years. Thus, naturally occurring antibodies do not protect CF patients from P. aeruginosa infection, and opsonic quality of serum antibodies deteriorates as infection becomes established.
Adolescent↗
Progression of pulmonary disease after disappearance of Pseudomonas in cystic fibrosis.
Once cystic fibrosis (CF) patients become chronically colonized, eradication of Pseudomonas aeruginosa (PA) is rare. We report five patients, each colonized for at least 6 yr, whose subsequent cultures did not reveal PA or any other gram-negative pathogen for at least 2 yr. Two patients harbored yeast, normal throat flora, and occasional colonies of Aspergillus fumigatus, but no PA, Haemophilus influenzae, or other gram-negative pathogens. In two patients, sputum cultures revealed Staphylococcus aureus. Sputum smear showed no gram-negative organisms in any patient. Antipseudomonal antibody titers in all patients decreased during the noncolonized period. However, titers increased in four other CF patients who had continued PA colonization. Despite disappearance of PA, four of five patients had clinical progression of lung disease with deterioration of FEV1. We conclude that (1) PA, even after it has chronically colonized the airways of CF patients, can occasionally disappear; and (2) lung disease can progress despite the disappearance of PA. Thus, the elimination of a milieu favorable to PA, such as might be anticipated with therapy directed at the basic defect, may not be sufficient to halt the pulmonary disease progression in CF.
Adult↗
Efficacy of the Flutter device for airway mucus clearance in patients with cystic fibrosis.
The Flutter is a handheld device designed to facilitate clearance of mucus in hypersecretory lung disorders. Exhalation through the Flutter results in oscillations of expiratory pressure and airflow, which vibrate the airway walls (loosening mucus), decrease the collapsibility of the airways, and accelerate airflow, facilitating movement of mucus up the airways. We studied 18 patients with cystic fibrosis and mild to moderate lung disease to determine the efficacy of the Flutter in clearing mucus from the airways. The amount of sputum expectorated (measured by weight) when the Flutter was used was compared with the amount expectorated with vigorous voluntary coughing and with postural drainage (chest percussion and vibration). The amount of sputum expectorated by subjects using the Flutter was more than three times the amount expectorated with either voluntary cough or postural drainage (p < 0.001). There were no adverse effects. The Flutter is simple to use, inexpensive, and fully portable, and once the patient and family are instructed in its use, it does not require the assistance of a caregiver. For hospitalized patients, elimination of the need for a therapist could reduce health care costs. Long-term studies of the use of the Flutter seem justified to determine its effects on pulmonary function and outcome.
Adolescent↗
Erosion of the wall of the frontal sinus caused by mucopyocele in cystic fibrosis.
Three patients with cystic fibrosis had complete erosion of one of the walls of a frontal sinus caused by a mucopyocele. Only fibrous tissue then separated the purulent contents of the sinus from the orbit or central nervous system. Initial surgery was unsuccessful, but two patients have remained free of symptoms after a second obliterating procedure. Sinus mucocele must be excluded by appropriate radiographic techniques when patients with cystic fibrosis have severe frontal headache and acute ophthalmologic symptoms.
Adult↗
Maternal child-rearing behavior in three groups: cystic fibrosis, insulin-dependent diabetes mellitus, and healthy children.
Compared child-rearing behaviors among mothers of children (ages 4-14) with cystic fibrosis (CF) (N = 26), insulin-dependent diabetes mellitus (IDDM) (N = 26), and mothers of physically healthy children (N = 26), on six domains, including involvement, limit setting, responsiveness, reasoning and guidance, free expression, and intimacy using the Iowa Parent Behavior Inventory. Maternal Reports of their child-rearing behavior were comparable across the three groups with one exception: Mothers of children with chronic illnesses (CF and IDDM) were significantly less likely to set limits than mothers of healthy children. The present findings are consistent with those of other studies that have identified few differences in child-rearing practices between mothers of children with chronic illnesses and mothers of healthy children. Future research should identify situation-specific parenting tasks unique to childhood chronic illness.
Adolescent↗
Spontaneous bacterial peritonitis in cystic fibrosis.
Bacterial peritonitis presents with classic symptoms of fever and abdominal pain. Some patients, however, are completely asymptomatic. Death in the short term is considerable, especially in patients with alcoholic cirrhosis. Cystic fibrosis patients occasionally develop biliary cirrhosis and may have secondary hypersplenism, varices, and ascites. These patients should be at risk for spontaneous bacterial peritonitis. Spontaneous bacterial peritonitis is described in two patients with longstanding hepatic cirrhosis secondary to cystic fibrosis. Both had required splenectomy for complications of portal hypertension. This is a previously unreported, but potentially fatal, complication of cystic fibrosis liver disease. Early diagnostic paracentesis is essential so that appropriate acute management, including antimicrobial treatment can be started. In the long term, these patients deserve immediate paracentesis for any evidence of recurrence. Whether the patient is treated with chronic (continuous) antimicrobial prophylaxis or only receives antimicrobial treatment during periods when bacteraemia is possible (for example, dental work, bronchoscopy), it would seem reasonable in patients with cystic fibrosis to use a wide spectrum antimicrobial agent with activity against Pseudomonas aeruginosa, other common Gram negative organisms, and Staphylococcus aureus.
Adolescent↗
Restoration of exocrine pancreatic function following pancreas-liver-kidney transplantation in a cystic fibrosis patient.
Pancreatic transplantation for endocrine replacement is well-established for insulin-dependent diabetes mellitus. Exocrine pancreatic function after pancreas transplantation has been maintained after orthotopic cluster transplants for malignancy, and restoration of adequate exocrine function in a previously deficient patient has been reported in a patient with chronic pancreatitis who developed labile diabetes and steatorrhea after pancreatectomy. We performed a triple organ transplant (pancreas, liver and kidney) in a patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to cystic fibrosis (CF) after he developed hepatic and renal failure. Pancreatic exocrine secretions were drained enterically to the jejunum. At 24-month follow-up, malabsorption is absent. The 3-day stool fat, stool trypsin and chymotrypsin are normal. Serum carotene is within the normal range. Exocrine pancreatic insufficiency in CF patients can be corrected by pancreas transplantation. However, routine use in CF is precluded by the risks of surgery and immunosuppression. For diabetic patients with pancreatic exocrine insufficiency who require another organ transplant (e.g., lung, liver, or kidney), simultaneous pancreas transplantation with the exocrine secretions directed into the upper gastrointestinal tract should be considered.
Adult↗
Multiplex PCR amplification from the CFTR gene using DNA prepared from buccal brushes/swabs.
Traditionally, DNA used for PCR-based diagnostic analysis has originated from white cells fractionated from whole blood. Although this method yields substantial quantities of DNA, there are some drawbacks to the procedure, including the inconvenience of drawing blood, risk of exposure to blood-borne pathogens, liquid sample handling, and the somewhat involved extraction procedure. Alternatively, DNA for genetic diagnosis has been derived from finger stick blood samples, hair roots, cheek scrapings, and urine samples. Oral saline rinses have also been used extensively as a means of collecting buccal epithelial cells as a DNA source. However, this method still requires liquid sample handling. Herein, we present our results involving the rapid extraction of DNA from buccal cells collected on cytology brushes and swabs for use in PCR reactions, specifically the multiplex amplification of 5 exons within the CFTR gene. The quality of DNA isolated from buccal cells, collected in this manner, has been sufficient to reproducibly support multiplex amplification. Cheek cell samples and the DNA prepared from them as described here are highly stable. The success rate of PCR amplification on DNA prepared from buccal cells is 99%. In a blind study comparing the analysis of 12 mutations responsible for cystic fibrosis in multiplex products amplified with DNA from both blood and buccal cell samples from 464 individuals, there was 100% correlation of results for blood and cheek cell DNA, validating the use of DNA extracted from cheek cells collected on cytology brushes for use in genetic testing.
Base Sequence↗
Characterization of an intron 12 splice donor mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
Cystic fibrosis, the most common lethal genetic disease in the white population, is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Analysis of DNA from a pancreatic insufficient patient by chemical mismatch cleavage and subsequent DNA sequencing led to the identification of a potential splice mutation in the CFTR gene. A transition of the invariant guanosine to adenosine (1898 + 1G > A) was found at the splice donor site of intron 12. To determine the effect of this mutation on the patient's CFTR transcripts, RNA from the nasal epithelium was reverse transcribed and amplified by the polymerase chain reaction (RT-PCR). Direct sequencing of the PCR products revealed that the transcript from the chromosome with the 1898 + 1G > A mutation had skipped exon 12 entirely, resulting in a joining of exons 11 and 13. Deletion of exon 12 results in the removal of a highly conserved region which encodes the Walker B consensus sequence of the first nucleotide-binding fold of CFTR.
Adult↗
Use of nonmedical treatment by cystic fibrosis patients.
To determine frequency, perceived effectiveness, and cost of religious, physical, and other nonmedical practices, we interviewed all (n = 402; 100% participation) of our cystic fibrosis patients/families [age, 0-45 (median, 18) years]. At least one type of nonmedical therapy was used by/on 264 (66%), two-thirds of which was religious. Most respondents perceived benefit (e.g., group prayer, 95%; religious articles, 81%; chiropractic, 69%). Only 17 (4.2%) invested over $200 lifetime (minimal compared with medical costs). These treatments, apparently used by most patients/families, rarely interfered with medical care. Physician openness and empathy toward patients' beliefs might enhance rapport and facilitate discussion of possible helpful or adverse effects of nonmedical treatment.
Adolescent↗
Left thyrocervical trunk bronchial artery supplying right lung: source of recurrent hemoptysis in cystic fibrosis.
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Adult↗
The nasal response to exercise in patients with cystic fibrosis.
This study has evaluated the nasal response to exercise in patients with cystic fibrosis (CF), a genetic disease in which factors such as chronic lung disease and/or nasal polyposis might be anticipated to modify nasal function responses. Measurements of nasal resistance (NAR) by posterior rhinomanometry and specific airway resistance (sRAW) were made before and 1, 5, 10, and 30 min after a 4-min period of exhausting legwork exercise (50% predicted maximal) in 19 CF patients (aged 11-29 years) and 10 healthy subjects (aged 11-31 years). One minute after exercise, healthy subjects showed a 54 +/- 5% (mean +/- SEM; standard error of the mean) relative fall from baseline in NAR and CF patients showed a 31 +/- 8% relative fall from baseline (p < 0.05). There were no significant differences in the magnitude or pattern of recovery in NAR after exercise (1 to 30 min) between the groups, largely because of the variability in NAR responses in CF patients. Exercise did not result in significant changes in sRAW in either group. We also found that a history or presence of nasal polyposis does not significantly affect functional nasal responses to exercise. Our conclusion is that the CF genotype and its airway sequelae do not substantively affect the control of the nasal response to exercise.
Adolescent↗
Longitudinal serum IgG response to Pseudomonas cepacia surface antigens in cystic fibrosis.
In cystic fibrosis (CF), serum antibody against surface antigens of Pseudomonas aeruginosa is detected only after colonization. Since pulmonary acquisition of P. cepacia usually follows colonization with P. aeruginosa and since P. aeruginosa-colonized patients with CF have demonstrable antibody against outer membrane proteins of P. cepacia, it appears that acquisition of the latter organism occurs in the presence of specific serum antibody. To test this hypothesis, serum obtained from six P. aeruginosa-colonized patients 4 and 2 years prior to and 3 months and 2 years after P. cepacia colonization were assayed for total and specific IgG to P. cepacia outer membrane components. Four patients demonstrated 6-fold or greater increases in specific IgG titers to whole outer membranes following colonization. By immunoblot, all patients had demonstrable serum IgG against the 27- and 36-kDa outer membrane proteins of P. cepacia 4 and 2 years prior to colonization. Immunoblots after P. cepacia acquisition demonstrated an intensification of the 28- and 36-kDa bands and the appearance of antibody to a very low molecular weight compound which was not hydrolyzed by proteinase K and was present in purified LPS. These observations suggest that low serum titers of antibody against two P. cepacia outer membrane proteins are present in patients with CF prior to P. cepacia colonization, and that these antibodies fail to protect for intrinsic or extrinsic reasons.
Adolescent↗
The action of halothane on stimulus-secretion coupling in clonal (GH3) pituitary cells.
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Animals↗