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Biomedical subjects

A G Davidson

Publications and source records attributed to A G Davidson.

At least 19 recordsLinked to original sources
PubMed2001

Infection with Burkholderia cepacia complex genomovars in patients with cystic fibrosis: virulent transmissible strains of genomovar III can replace Burkholderia multivorans.

Infection with Burkholderia cepacia complex in patients with cystic fibrosis (CF) results in highly variable clinical outcomes. The purpose of this study was to determine if there are genomovar-specific disparities in transmission and disease severity. B. cepacia complex was recovered from 62 patients with CF on > or =1 occasions (genomovar III, 46 patients; genomovar II [B. multivorans], 19 patients; genomovar IV [B. stabilis], 1 patient; genomovar V [B. vietnamiensis], 1 patient; and an unclassified B. cepacia complex strain, 1 patient). Patient-to-patient spread was observed with B. cepacia genomovar III, but not with B. multivorans. Genomovar III strains replaced B. multivorans in 6 patients. Genomovar III strains were also associated with a poor clinical course and high mortality. Infection control practices should be designed with knowledge about B. cepacia complex genomovar status; patients infected with transmissible genomovar III strains should not be cohorted with patients infected with B. multivorans and other B. cepacia genomovars.

Adolescent↗
PubMed2001

Long-term comparative trial of positive expiratory pressure versus oscillating positive expiratory pressure (flutter) physiotherapy in the treatment of cystic fibrosis.

OBJECTIVE: The objective was to evaluate the long-term effects of physiotherapy with an oscillating positive pressure device ("flutter") compared with physiotherapy with the use of a positive expiratory pressure (PEP) mask in patients with cystic fibrosis (CF). STUDY DESIGN: Forty children with CF were randomly assigned to performing physiotherapy with the PEP mask or the flutter device for 1 year. Clinical status, pulmonary function, and compliance were measured at regular intervals throughout the study. RESULTS: The flutter group demonstrated a greater mean annual rate of decline in forced vital capacity compared with the PEP group (-8.62 +/- 15.5 vs 0.06 +/- 7.9; P =.05) with a similar trend in forced expiratory volume in 1 second (-10.95 +/- 19.96 vs -1.24 +/- 9.9; P =.08). There was a significant decline in Huang scores (P =.05), increased hospitalizations (18 vs 5; P =.03), and antibiotic use in the flutter group. CONCLUSION: Flutter was not as effective in maintaining pulmonary function in this group of patients with CF compared with PEP and was more costly because of the increased number of hospitalizations and antibiotic use.

Adolescent↗
PubMed2000

An unusual presentation of doxycycline-induced photosensitivity.

Photoonycholysis in association with a generalized phototoxic reaction or as an isolated event is a well-recognized complication of the tetracycline group of antibiotics. We describe a 14-year-old white girl with cystic fibrosis who developed photoonycholysis of all 20 nails while receiving treatment with doxycycline. Pediatricians who prescribe tetracyclines should be aware of this potential complication.

Adolescent↗
PubMed1999

Burkholderia cepacia in cystic fibrosis. Variable disease course.

Variable clinical course has been reported with the acquisition of Burkholderia cepacia in patients who have cystic fibrosis (CF). We hypothesized that the perceived worsening with B. cepacia may reflect the underlying severity of pulmonary disease at the time of acquisition. To test this hypothesis, we matched CF patients colonized with B. cepacia with CF patients not colonized with the organism. Two-year pre- and postacquisition data and long-term data were compared. Patients were matched for gender, age (+/- 1 yr), height (+/- 5 cm), weight (+/- 8 kg), percent predicted forced expiratory volume in one second (% pred FEV(1)) (+/- 10%), and pancreatic sufficiency status. Differences in rates of change pre- and postacquisition for FEV(1), FVC, weight, and frequency of intravenous courses were compared within pairs with the Wilcoxon signed rank test. Two-year and long-term survival was compared within pairs with the McNemar test. No significant differences were observed in mean annual rates of change in weight (0.33 and -0.28 kg/yr), % pred FEV(1) (-0.36 and -1.74%/yr), and percent predicted forced vital capacity (% pred FVC) (-3.80 and -2.32%/yr) between B. cepacia and control pairs in 2-yr and long-term postacquisition interval, respectively. Similar rates of change were noted for pre- to postacquisition intervals within pairs for weight (0.17 kg/yr), % pred FEV(1) (-0.16%/yr), % pred FVC (5.02 %/yr). There was a significantly higher rate of intravenous antibiotic courses in B. cepacia cases in the 2-yr and long-term postacquisition interval. Higher mortality was observed in the B. cepacia cases in the long term (p < 0.05). We conclude that colonization with B. cepacia does not necessarily adversely affect pulmonary status, but is associated with reduced long term survival. Whereas previous associations may be attributed to a propensity to colonize those who had more advanced disease, specific strain types of B. cepacia may have enhanced pathogenicity.

Adolescent↗
PubMed1998

Evidence for an early G1 ionic event necessary for cell cycle progression and survival in the MCF-7 human breast carcinoma cell line.

The mechanism of the G0/G1 arrest and inhibition of proliferation by quinidine, a potassium channel blocker, was investigated in a tissue culture cell line, MCF-7, derived from a human breast carcinoma. The earliest measurable effect of quinidine on the cell cycle was a decrease in the fraction of cells in S phase at 12 hr, followed by the accumulation of cells in G1/G0 phases at 30 hr. Arrest and release of the cell cycle established quinidine as a cell synchronization agent, with a site of arrest in early G1 preceding the lovastatin G1 arrest site by 5-6 hr. There was a close correspondence among the concentration-dependent arrest by quinidine in G1, depolarization of the membrane potential, and the inhibition of ATP-sensitive potassium currents, supporting a model in which hyperpolarization of the membrane potential and progression through G1 are functionally linked. Furthermore, the G1 arrest by quinidine was overcome by valinomycin, a potassium ionophore that hyperpolarized the membrane potential in the presence of quinidine. With sustained exposure of MCF-7 cells to quinidine, expression of the Ki67 antigen, a marker for cells in cycle, decreased, and apoptotic and necrotic cell death ensued. We conclude that MCF-7 cells that fail to progress through the quinidine-arrest site in G1 die.

Anti-Arrhythmia Agents↗
PubMed1997

Long-term comparative trial of conventional postural drainage and percussion versus positive expiratory pressure physiotherapy in the treatment of cystic fibrosis.

OBJECTIVE: We report the results of a long-term comparative trial of physiotherapy by the positive expiratory pressure (PEP) technique with a PEP mask (Astra Meditec) versus conventional postural drainage and percussion (PD&P). Forty patients, ages 6 to 17 years, with Shwachman scores between 52 and 93, attending the cystic fibrosis clinic were enrolled in the study and randomly assigned to one of two groups. Group A (control) continued to perform physiotherapy by using PD&P for a 1-year period, whereas patients assigned to group B performed physiotherapy with the PEP technique for the same period. Compliance with physiotherapy was closely monitored for both groups throughout the study. Clinical status and pulmonary function (forced vital capacity [FVC], FEV1, and FEF25-75) were measured at 3-month intervals. Group B (PEP) demonstrated improved pulmonary function in all parameters as measured by change in percent predicted value for age, gender, and height. The changes in pulmonary function over the study period were: FVC, +6.57; FEV1, +5.98; and FEF25-75, +3.32. This improvement was significantly different from that of group A (PD&P) whose pulmonary function declined in all parameters (FVC, -2.17; FEV1, -2.28; FEF25-75, -0.24). The differences between treatment groups were statistically significant for the changes in FVC (p = 0.02) and FEV(1) (p = 0.04). Our results indicate that for our patients with cystic fibrosis, pulmonary physiotherapy with the PEP technique was superior to conventional physiotherapy with the PD&P technique.

Adolescent↗
PubMed1996

Treatment of recurrent hemoptysis in a child with cystic fibrosis by repeated bronchial artery embolizations and long-term tranexamic acid.

The course of a 12-year-old girl with cystic fibrosis (CF) and with recurrent hemoptysis since age 8 years is described. Conservative measures failed to control her bleeding. Hemoptysis was only partially controlled by repeated bronchial arterial embolizations. However, the addition of tranexamic acid (TXA) resulted in complete cessation of bleeding. Attempts to withdraw TXA therapy resulted in recurrence of hemoptysis; this patient has, therefore, been continuously maintained on this therapy for the past 4 years. No side effects of long-term TXA treatment have been noted.

Antifibrinolytic Agents↗
PubMed1996

Airway clearance techniques in the treatment of cystic fibrosis.

Airway clearance is a major component of the management of cystic fibrosis. In North America, the airway clearance technique of choice has been physiotherapy using postural drainage combined with chest percussion, deep breathing and vibration. The disadvantages of this technique, the introduction of newer airway clearance techniques, and a greater emphasis on exercise has sparked a growing trend to prescribing individualized programs combining exercise with strategies adapted to the needs of each patient.

Airway Obstruction↗
PubMed1995

Selective media for isolation of Burkholderia (Pseudomonas) cepacia from the respiratory secretions of patients with cystic fibrosis.

One hundred and six specimens from 90 patients with cystic fibrosis were evaluated for the presence of Burkholderia cepacia using a current routine diagnostic protocol as well as a research protocol involving polymyxin B-MacConkey agar without crystal violet, PC agar, OFPVL agar, and a selective brain-heart infusion broth. Ten specimens from eight patients (8.9%) were positive by any method. The selective enrichment broth was the only medium that yielded B cepacia from all 10 positive samples, although the routine protocol was successful for eight of these. Transient carriage was identified in one patient. Epidemiological studies may be better served by the use of selective enrichment rather than selective solid media alone. Carrier status for B cepacia requires more strict definition if positive carrier status is to be accepted as having medical importance.

Adolescent↗
PubMed1994

Altered retinoblastoma protein expression and prognosis in early-stage non-small-cell lung carcinoma.

BACKGROUND: Altered retinoblastoma (RB [also known as RB1]) gene expression was initially found in a small cohort study to occur in five (22%) of 23 patients with primary stage I and II non-small-cell lung carcinomas (NSCLCs). Putative mutation of the p53 gene (also known as TP53) has also been found to occur frequently in stage I and II NSCLCs and to be associated with more aggressive disease and a poorer prognosis. PURPOSE: Our purpose was to determine the Rb protein status in the same cohort that had been previously studied for their p53 protein status and to document whether loss of Rb protein expression was also an important factor in overall survival. METHODS: One hundred one stage I or II NSCLC specimens were analyzed by immunohistochemical staining. These paraffin-embedded tumor sections were obtained from individual paraffin blocks prepared for each patient in the previous study. Patient survival status was obtained from hospital and tumor registry records. RESULTS: Altered Rb protein expression was found in 24 of 101 stage I and II NSCLCs. The median survival was 32 months for patients with Rb-positive (Rb+) tumors and 18 months for individuals in whom expression of Rb protein was absent or altered (Rb-) in tumor cells. Log-rank analysis of the differences in overall survival was statistically significant (P = .007). When these results were combined with the p53 status in the same tumor, the median survival was 12 months for those individuals who had theoretically the worst pattern (Rb-/p53+) and 46 months for those patients with theoretically the best pattern (Rb+/p53-) (P < .001). The Rb+ and Rb- groups in this cohort were well balanced with respect to the distribution of age, disease stage, histologic types, p53 status, and sex. Using a multivariate proportional hazards regression model, both altered Rb and p53 status were found to be significantly associated with poor prognosis (P = .005 and .012, respectively) in the overall cohort. CONCLUSION: Altered Rb protein expression is an independent prognostic marker for overall decreased survival in early-stage NSCLC as detected by absence of nuclear Rb protein staining. There appears to be a poorer prognosis when loss of Rb protein function and mutated p53 protein occur in the same tumor. IMPLICATIONS: If these findings can be confirmed in larger prospective studies, the results would suggest that both the Rb and p53 status should be utilized as independent prognostic factors in early-stage NSCLC.

Adenocarcinoma↗
PubMed1994

Potential application of p53 as an intermediate biomarker in Barrett's esophagus.

Diagnosis of the neoplastic progression in Barrett's esophagus using the histologic classification of dysplasia is frequently difficult. The tumor suppressor protein p53, when mutated, confers a promoter effect on cell growth. The purpose of this study was to evaluate the applicability of p53 as an intermediate biomarker of malignancy in Barrett's esophagus. Archival analysis of 100 biopsy specimens of Barrett's esophagus and 10 esophageal adenocarcinomas were compared with 35 chronic esophagitis biopsy specimens. Immunocytochemistry using an anti-p53 monoclonal antibody was performed and elevated immunoreactivity quantitated microscopically. Data were analyzed using a logistic regression model. Significant p53 immunoreactivity occurred as follows: chronic esophagitis (0%), Barrett's esophagus without dysplasia (10%), with low-grade dysplasia (60%), with high-grade dysplasia (100%), and adenocarcinoma (70%). All cases of Barrett's esophagus were significantly immunoreactive when compared with the chronic esophagitis cases (p = 0.001). There was an increase in p53 immunoreactivity as the histologic classification progressed toward adenocarcinoma (p = 0.001). Progression to high-grade dysplasia may be predicted based on p53 immunoreactivity. These findings suggest a role for p53 as an intermediate biomarker in Barrett's esophagus.

Adenocarcinoma↗
PubMed1994

Bone marrow transplantation in Gaucher's disease: effect of mixed chimeric state.

The effective dose and schedule of enzyme replacement therapy for Gaucher's disease have not been definitely established. We report a case of mixed chimeric state in an allogeneic BMT patient and followed her clinical and laboratory progress. The result shows that a low but sustained glucocerebrosidase level may provide symptomatic relief for this lysosomal disorder.

Bone Marrow Transplantation↗
PubMed1993

Oral zinc therapy in the treatment of alpha-mannosidosis.

Human alpha-mannosidosis is a lysosomal storage disorder characterized by mental retardation, dysostosis multiplex, and hepatosplenomegaly. Deficiency of the enzyme leads to accumulation of mannose-rich glycoconjugates in tissues. Zinc sulphate has been shown to stimulate alpha-mannosidase activity in vitro. Oral zinc therapy was attempted on a 4-year-old boy with alpha-mannosidosis for 3 years. After almost 10 years of follow-up on and off zinc therapy, we must conclude that oral zinc does not substantially affect the clinical course of alpha-mannosidosis.

Administration, Oral↗
PubMed1993

Pseudomonas aeruginosa colonization of the gastrointestinal tract in patients with cystic fibrosis.

Respiratory and fecal specimens from 111 patients with cystic fibrosis (CF) were cultured on 394 occasions to determine which site Pseudomonas aeruginosa colonizes first. By an enrichment and selection culture technique, P. aeruginosa was recovered from fecal cultures in 21 (42%) of 50 respiratory tract-positive patients but from only 3 (6.3%) of 48 respiratory tract-negative patients and from 1 (2.2%) of 45 control subjects. In 4 (22%) of the 18 patients who became culture-positive during the study, P. aeruginosa was recovered from a fecal specimen before respiratory colonization. Only 1 of these 4 became persistently colonized with P. aeruginosa in the respiratory tract; however, the serotype of the respiratory isolate was different from that of the fecal isolate. P. aeruginosa is recovered rarely from the feces of patients with CF who are culture-negative in the respiratory tract. In patients with CF, primary colonization with P. aeruginosa probably occurs in the respiratory tract.

Adolescent↗
PubMed1993

Barrett's esophagus in children with cystic fibrosis: not a coincidental association.

Barrett's esophagus (BE) is a premalignant condition, and a recognized complication of severe gastroesophageal (GE) reflux. Children with cystic fibrosis (CF) have a marked predilection to develop GE reflux, but Barrett's esophagus is one complication of GE reflux not previously described in CF. We describe in detail two adolescents with CF who were found to have Barrett's esophagus, and mention three other cases. The presence of Barrett's esophagus in CF patients may be missed because GE reflux is often relatively silent in CF, because patients may consider mild upper gastrointestinal (GI) symptoms as "part of CF," and because of the nature of Barrett's epithelium itself. Upper gastrointestinal (GI) endoscopy with documentation of landmarks and multiple targeted biopsies should be performed in children with CF with even mild symptoms of GE reflux or an abnormal 24 h intra-esophageal pH study. Any biopsies containing columnar epithelium should be stained with Alcian blue at pH 2.5 to look for goblet cell metaplasia, i.e., Barrett's esophagus. Children with CF may be a high-risk group for development of Barrett's esophagus and its complications, especially given the increased survival in CF.

Adolescent↗
PubMed1992

Accumulation of p53 protein correlates with a poor prognosis in human lung cancer.

Mutations in the gene coding for the p53 tumor suppressor protein are common in a variety of human cancers. To assess the role of a putative mutated p53 protein in human lung cancer, a monoclonal antibody recognizing it was used in an immunoperoxidase detection system. A total of 114 cases of Stage I and II adenocarcinomas and squamous cell carcinomas were studied. The staining pattern was always intranuclear and heterogeneous. When the median or mean survival time was compared between cases, p53 accumulation had a statistically significant negative prognostic value. This was supported by a Kaplan-Meier survival plot of p53 producers and nonproducers. In 7 of 24 Stage II cases that were negative for p53 in the primary tumor, metastatic regional lymph nodes were p53-positive. These latter cases had greatly reduced survival times. Thus, p53 accumulation in primary tumors (and regional lymph nodes) may identify a subgroup of lung cancer patients with a prognosis of more aggressive disease.

Adenocarcinoma↗