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Biomedical subjects

E Tullis

Publications and source records attributed to E Tullis.

16 recordsLinked to original sources
PubMed2006

Predictors of pulmonary exacerbations in patients with cystic fibrosis infected with multi-resistant bacteria.

BACKGROUND: This study examined characteristics of adult and adolescent patients with cystic fibrosis (CF) to determine factors associated with an increased risk of pulmonary exacerbations. METHODS: 249 patients with CF infected with multidrug resistant bacteria were recruited and prospectively followed for up to 4.5 years until they experienced a pulmonary exacerbation severe enough to require intravenous antibiotics. Multivariable regression analyses were used to compare the characteristics of patients who experienced an exacerbation with those who did not. RESULTS: 124 of the 249 patients (50%) developed a pulmonary exacerbation during the first year and 154 (62%) experienced an exacerbation during the 4.5 year study period. Factors predictive of exacerbations in a multivariable survival model were younger age (OR 0.98, 95% CI 0.96 to 0.99), female sex (OR 1.45, 95% CI 1.07 to 1.95), lower forced expiratory volume in 1 second (FEV(1)) (OR 0.98, 95% CI 0.97 to 0.99), and a previous history of multiple pulmonary exacerbations (OR 3.16, 95% CI 1.93 to 5.17). Chronic use of inhaled corticosteroids was associated with an increased risk of exacerbation (OR 1.92, 95% CI 1.00 to 3.71) during the first study year. CONCLUSIONS: Patients who experience pulmonary exacerbations are more likely to be younger, female, using inhaled steroids, have a lower FEV(1), and a history of multiple previous exacerbations. It is hoped that knowledge of these risk factors will allow better identification and closer monitoring of patients who are at high risk of exacerbations.

Adolescent↗
PubMed2005

The prevalence and clinical characteristics of cystic fibrosis in South Asian Canadian immigrants.

BACKGROUND: Cystic fibrosis (CF) is considered to be rare among individuals from the Indian subcontinent. Furthermore, affected individuals are reported to experience a more severe clinical course. AIMS: It was hypothesised that CF is under diagnosed in people of South Asian origin and therefore the prevalence may be higher than previously estimated. METHODS: The prevalence of CF in the South Asian and in the general population living in the same geographic region (Metropolitan Toronto) were compared between 1996 and 2001. Population data were obtained from the Canadian census survey. CF phenotype and genotype data were obtained from the Toronto CF database. RESULTS: Among 381 patients with CF, 15 were of South Asian descent. The age related prevalence of CF among the South Asian and general populations was: 0-14 years, 1:9200 versus 1:6600; 15-24 years, 1:13,200 versus 1:7600; older than 25 years, 1:56,600 versus 1:12,400. Age at diagnosis, duration and severity of symptoms at diagnosis, current nutritional status, and FEV(1) were similar in the two groups. While not significant, FEV1 tended to be lower (48% versus 57% predicted) among adult South Asians, compared to the general CF population. Also, the percentage with pancreatic sufficiency was higher (27% versus 16%) and the frequency of DeltaF508 allele was lower (50% versus 65.1%). CONCLUSIONS: These data suggest that the prevalence and natural history of CF in South Asians is similar to that among individuals of European origin. The relatively lower prevalence among older South Asians may reflect an improving recognition of CF in this ethnic subgroup.

Adolescent↗
PubMed2003

Molecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas.

BACKGROUND AND AIMS: We tested the hypothesis that the actual or predicted consequences of mutations in the cystic fibrosis transmembrane regulator gene correlate with the pancreatic phenotype and with measures of quantitative exocrine pancreatic function. METHODS: We assessed 742 patients with cystic fibrosis for whom genotype and clinical data were available. At diagnosis, 610 were pancreatic insufficient, 110 were pancreatic sufficient, and 22 pancreatic sufficient patients progressed to pancreatic insufficiency after diagnosis. RESULTS: We identified mutations on both alleles in 633 patients (85.3%), on one allele in 95 (12.8%), and on neither allele in 14 (1.9%). Seventy six different mutations were identified. The most common mutation was DeltaF508 (71.3%) followed by G551D (2.9%), G542X (2.3%), 621+1G-->T (1.2%), and W1282X (1.2%). Patients were categorized into five classes according to the predicted functional consequences of each mutation. Over 95% of patients with severe class I, II, and III mutations were pancreatic insufficient or progressed to pancreatic insufficiency. In contrast, patients with mild class IV and V mutations were consistently pancreatic sufficient. In all but four cases each genotype correlated exclusively with the pancreatic phenotype. Quantitative data of acinar and ductular secretion were available in 93 patients. Patients with mutations belonging to classes I, II, and III had greatly reduced acinar and ductular function compared with those with class IV or V mutations. CONCLUSION: The predicted or known functional consequences of specific mutant alleles correlate with the severity of pancreatic disease in cystic fibrosis.

Child↗
PubMed2001

Treatment of vitamin K deficiency in cystic fibrosis: Effectiveness of a daily fat-soluble vitamin combination.

OBJECTIVE: Patients with cystic fibrosis (CF) and pancreatic insufficiency (PI) commonly have vitamin K deficiency, and those with CF-associated liver disease (CFLD) have universal vitamin K deficiency. We evaluated the effectiveness of an oral fat-soluble vitamin combination (ADEKs) to treat patients with vitamin K deficiency. STUDY DESIGN: Patients with PI and CF (mean age, 15 years; range, 0.6 to 46 years) including 6 with advanced CFLD were prospectively enrolled in a study of a fat-soluble vitamin combination taken on a daily basis. None had received vitamin K supplementation for at least 4 months before the study. Fat-soluble vitamin combination supplementation was given for a minimum of 4 months; the mean vitamin K intake was 0.18 mg/d (SD = 0.1, range, 0 to 0.3). The primary outcome was change in plasma PIVKA-II (prothrombin in vitamin K absence). RESULTS: Before supplementation 58 (81%) of 72 patients had abnormal PIVKA-II levels (>2.9 ng/mL). After supplementation 29 (40%) had abnormal PIVKA-II levels (P =.001). All 6 patients with advanced CFLD had abnormal PIVKA-II levels (median, range of 20.8, 5.5 to 55 ng/mL) before treatment, which corrected to normal in 50% (4.1, 2.1 to 65 ng/mL). Four patients, 2 with CFLD, had a prolonged prothrombin time (>13.5 seconds) at both time periods. CONCLUSIONS: An oral fat-soluble vitamin combination with a modest amount of vitamin K can, as a daily supplement, improve the PIVKA-II levels in patients with PI and CF.

Adolescent↗
PubMed2001

Direct and indirect bacterial killing functions of neutrophil defensins in lung explants.

Studies of the antimicrobial activity of neutrophil defensins have mostly been carried out in microbiological media, and their effects on the host defense in physiological conditions are unclear. We examined 1) the antibacterial activity of defensins in physiological media with and without lung tissue present, 2) the effect of defensins on hydrogen peroxide (H(2)O(2)) production by lung tissue that had been exposed to bacteria, and 3) the effect of diphenyleneiodonium (DPI), an inhibitor of reactive oxygen species formation, on the antibacterial activity of defensins in the presence of lung tissue. Defensins were incubated with Escherichia coli or Pseudomonas aeruginosa in the absence or presence of primary cultured mouse lung explants. Defensins reduced bacterial counts by approximately 65-fold and approximately 25-fold, respectively, at 48 h; bacterial counts were further decreased by approximately 600-fold and approximately 12,000-fold, respectively, in the presence of lung tissue. Defensins induced H(2)O(2) production by lung tissue, and the rate of killing of E. coli by defensins was reduced by approximately 2,500-fold in the presence of 10 microM DPI. We conclude that defensins exert a significant antimicrobial effect under physiological conditions and that this effect is enhanced in the presence of lung tissue by a mechanism that involves the production of reactive oxygen species.

Animals↗
PubMed2001

Infection with Burkholderia cepacia in cystic fibrosis: outcome following lung transplantation.

As a result of concern over excessive mortality after lung transplantation, many transplant programs refuse to accept cystic fibrosis (CF) patients infected with Burkholderia cepacia. As a significant proportion of patients with CF in our community are infected with this organism, we have continued to provide lung transplantation as an option. A retrospective review was conducted of medical records of all patients with CF transplanted between March 1988 and September 1996. Fifty-six transplant procedures were performed in 53 recipients with CF between March 1988 and September 1996. Twenty-eight had B. cepacia isolated pretransplant and 25 remaining positive post-transplant. Of the 53 recipients, 19 have died (15 of 28 [54%] B. cepacia positive and 4 of 25 [16%] B. cepacia negative). B. cepacia was responsible for or involved in 14 deaths. Nine of the deaths occurred in the first 3 mo post-transplantation. One-year survival was 67% for B. cepacia positive patients and 92% for B. cepacia negative patients. Recent modifications in antimicrobial and immunosuppressive therapy since 1995 have resulted in no deaths early post-transplant in the last five patients transplanted. We conclude that early mortality in patients with CF infected with B. cepacia is significantly higher than in those not infected with B. cepacia. Modifications in post-transplant medical therapy may improve outcome.

Adult↗
PubMed2000

Challenges in the dietary treatment of cystic fibrosis related diabetes mellitus.

Cystic fibrosis related diabetes mellitus is an increasingly recognized problem as survival in patients with cystic fibrosis improves. In a 5 year retrospective study of 627 children and adults attending Toronto cystic fibrosis clinics, we identified 57 (9%) patients with cystic fibrosis related diabetes mellitus; four (1.3%) of 301 children (<18 years) and 53 (16%) of 326 adults. The development of this complication of cystic fibrosis is associated with increased mortality, deteriorations in both respiratory and nutritional status, and the development of late microvascular, but not macrovascular, diabetic complications. Unfortunately, systematic review of the literature provides few well designed studies that provide sound evidence for clinical practice. Recommendations are therefore often based on anecdote, rather than physiological or outcomes research. Dietary therapy combines the principles of the dietary management of both cystic fibrosis and diabetes mellitus, but emphasizes the need for a high energy diet (> 100% of recommended daily intake) in patients with cystic fibrosis related diabetes mellitus. The importance of calories from fat is emphasized, with no restriction on total carbohydrate intake. Insulin intake mirrors carbohydrate intake. Routine dietary therapy is straightforward, but challenges occur due to both complications of cystic fibrosis and advancing disease. If a patient with cystic fibrosis related diabetes mellitus is malnourished, overnight enteral tube feeding is often used, with an adjusted insulin regimen. There is a great need for both physiological and outcomes research to provide sound scientific evidence for the dietary treatment of cystic fibrosis related diabetes mellitus.

Cystic Fibrosis↗
PubMed2000

Cystic fibrosis. End-stage care in Canada.

OBJECTIVES: To determine the circumstances in which individuals with cystic fibrosis (CF) die, the role of different caregivers, and the extent of palliative care for CF patients. DESIGN: Mailed survey of CF physicians. SETTING: CF centers in Canada. PATIENTS: All CF deaths in 1996 known to centers in Canada. RESULTS: The mean age (+/- SD) at death of the 45 individuals included in the study was 25.8 +/- 13.5 years. The major cause of death was respiratory (34 patients; 75.5%). Nutritional concerns were common. Lung transplantation was considered in 42 patients (93.2%), with 7 patients (17.1%) being entered on a list, but it was carried out in only 2 patients (4.4%). Autopsies were performed on only 10 patients (22.2%). Most patients died in hospital (37 patients; 82.2%), and 7 patients (15.6%) died in ICUs while receiving intermittent positive-pressure ventilation. Palliative care was never discussed in 10 patients (25%). In a further 16 patients (40%), it was not discussed until the last month before death. CONCLUSIONS: Respiratory disease remains the most common cause of death in CF patients. Lung transplantation is frequently considered, but most patients die without having had a transplant. Discussions on end-of-life care could be considered sooner.

Adult↗
PubMed1999

Prevalence of vitamin K deficiency in cystic fibrosis.

BACKGROUND: Patients with cystic fibrosis (CF) are at risk of developing vitamin K deficiency because of pancreatic insufficiency, hepatobiliary disease, or both. OBJECTIVE: Our objective was to determine the prevalence of vitamin K deficiency in unsupplemented patients with CF and to identify risk factors that might be associated with the deficiency. DESIGN: Ninety-eight patients with CF-83 who were pancreatic insufficient (age: 15.2 +/- 10.7 y; range: 0.6-45.8 y), 15 who were pancreatic sufficient (age: 26.2 +/- 11.6 y; range: 6.5-45.3 y), and 62 healthy individuals (age: 16.2 +/- 12. 8 y; range: 1-45 y)-were studied prospectively. None had taken vitamin K supplements. Eight pancreatic-insufficient patients had advanced CF-associated liver disease. Plasma prothrombin in vitamin K absence (PIVKA-II) was measured by immunoassay. All control subjects had PIVKA-II concentrations <3 microg/L. RESULTS: Seventy-eight percent of pancreatic-insufficient patients had PIVKA-II concentrations >/=3 microg/L (22.8 +/- 35.7 microg/L). All patients with CF-associated liver disease had abnormal PIVKA-II concentrations. The mean PIVKA-II concentration of pancreatic-insufficient patients with liver disease was greater than that of those without liver disease (46.6 +/- 65.3 compared with 15. 3 +/- 26.1 microg/L; P < 0.05). Five pancreatic-sufficient patients had mildly elevated PIVKA-II concentrations. Six (7%) pancreatic insufficient patients (3 with CF-associated liver disease) had mildly prolonged prothrombin time but no clinical bleeding. There was no correlation between PIVKA-II concentrations and severity of fat malabsorption or antibiotic use. CONCLUSIONS: Vitamin K deficiency is common in unsupplemented patients with CF and pancreatic insufficiency and routine supplementation should be considered in all of these patients.

Adolescent↗
PubMed1998

The molecular basis of disease variability among cystic fibrosis patients carrying the 3849+10 kb C-->T mutation.

Disease severity varies among cystic fibrosis (CF) patients carrying the same CFTR genotype. Here we studied the mechanism underlying disease variability in individuals carrying a splicing CFTR mutation, 3849+10 kb C-->T. This mutation was shown to produce both correctly and aberrantly spliced CFTR transcripts containing an additional cryptic exon. Semiquantitative nondifferential RT-PCR showed considerable variability in the level (0-28%) of aberrantly spliced RNA transcribed from the 3849+10 kb C-->T mutation in nasal epithelium from 10 patients. A significant inverse correlation was found between the level of the aberrantly spliced CFTR transcripts and pulmonary function, expressed as FEV1 (r = 0.92, P < 0.0001). Patients with normal pulmonary function (FEV1 > 80% predicted) had lower levels of aberrantly spliced CFTR RNA (0 to 3%) than those with FEV1 < 80%, (9 to 28% aberrantly spliced RNA). Only aberrantly spliced CFTR RNA was detected in the lung of a patient with severe lung disease who underwent lung transplantation. Our results show that the severity of CF lung disease correlates with insufficiency of normal CFTR RNA. Thus, the regulation of alternative splice site selection may be an important mechanism underlying partial penetrance in CF. Further understanding of this regulation will contribute to potential therapy for patients carrying splicing mutations in human disease genes.

Adolescent↗
PubMed1998

Heterogeneity of reproductive tract abnormalities in men with absence of the vas deferens: role of cystic fibrosis transmembrane conductance regulator gene mutations.

OBJECTIVE: To determine if the types of reproductive tract abnormalities linked to absence of the vas deferens varies with the cystic fibrosis transmembrane conductance regulator (CFTR) genotype. DESIGN: Prospective data gathering. SETTING: University infertility clinic. PATIENT(S): Forty-six infertile men with absence of the scrotal vas deferens and no signs of cystic fibrosis. INTERVENTION(S): All had blood taken for CFTR gene analysis, 33 had scrotal ultrasounds, and 25 had transrectal ultrasounds. MAIN OUTCOME MEASURE(S): The frequency of testicular, seminal vesicle, and ampullae of the vas deferens malformations was compared between subgroups of men with two, one, or no CFTR gene mutations. RESULT(S): None (0 of 21) of the men with at least one CFTR gene mutations had normal ampullae of the vas or seminal vesicles bilaterally. Two (50%) of 4 men with no CFTR gene mutations had normal ampullae of the vas deferens bilaterally, and 50% had normal bilateral seminal vesicles (statistically significantly different). There was no correlation between testicular malformations and CFTR genotype. CONCLUSION(S): This study indicates that the severity of the malformations in the testis is unrelated to the CFTR genotype, whereas the frequency and severity of wolffian duct malformations are related directly to the CFTR genotype.

Cystic Fibrosis Transmembrane Conductance Regulato↗
PubMed1998

Uncertainty in the diagnosis of cystic fibrosis: possible role of in vivo nasal potential difference measurements.

The diagnosis of cystic fibrosis (CF) is not always certain, despite extensive clinical evaluation, multiple sweat chloride tests, and genotype analysis. We hypothesized that nasal transepithelial potential difference measurements have a useful role in this situation. In 11 patients without an established diagnosis of CF, results of simultaneous nasal potential difference (PD) and sweat chloride measurements were compared with those from control subjects, obligate CF heterozygotes, and patients with a confirmed diagnosis of CF. Two patients conformed to the PD profile for CF patients, whereas nine had values corresponding to those of the healthy control subjects. Subsequently the 5-thymidine (IVS8-5T) CF gene variant was identified in the two patients with abnormal PD measurements.

Adolescent↗
PubMed1992

The long-term effects of aerosol pentamidine on pulmonary function. The Toronto Aerosolized Pentamidine Study (TAPS) Group.

Aerosolized pentamidine (AP) has been widely used for prophylaxis of pneumocystis carinii pneumonia (PCP) since 1988. The objective of this study was to evaluate the long-term effects of AP on pulmonary function. Of 36 patients with AIDS who were receiving AP for secondary prophylaxis of PCP, 13 patients had been using AP continuously for more than 52 weeks. AP was given using a Fisoneb ultrasonic nebulizer with five loading doses of 60 mg over two weeks, followed by one dose of 60 mg every two weeks. Baseline PFT were TLC 92 +/- 14% pred, FVC 90 +/- 11% pred, FEV1 91 +/- 11% pred, FEF25-75 95 +/- 17% pred, and DLCO (corrected for hemoglobin) 70 +/- 22% pred. No significant change in TLC, FVC, FEV1, or DLCO was seen after 56 weeks of AP. There was a 20% fall in FEF25-75 seen after 56 weeks, which was statistically significant. However, the clinical significance of a fall of this magnitude in the FEF25-75 is uncertain. Similar results were seen in a smaller subset of patients who received AP for at least 76 weeks. Although the small sample size must be considered, this data suggests that there is no clinically significant change in pulmonary function associated with the use of AP for up to 76 weeks.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

What's involved in a program transfer between hospitals?

More hospitals are being forced to restructure in a bid to cope with financial constraints. One effective option is the transfer of clinical programs between facilities. The procedure is complicated and commands good leadership, negotiating skills, trust and a comprehensive understanding of the program being transferred. This article deals with the knowledge gained from the recent successful transfer of the Adult Cystic Fibrosis Program and its associated operating funds from one Toronto hospital to another.

Adult↗