| 1. |
- Castellani, Carlo, et al.
(author)
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Consensus on the use and interpretation of cystic fibrosis mutation analysis in clinical practice
- 2008
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In: Journal of Cystic Fibrosis. - : Elsevier BV. - 1569-1993 .- 1873-5010. ; 7:3, s. 179-96
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Journal article (peer-reviewed)abstract
- It is often challenging for the clinician interested in cystic fibrosis (CF) to interpret molecular genetic results, and to integrate them in the diagnostic process. The limitations of genotyping technology, the choice of mutations to be tested, and the clinical context in which the test is administered can all influence how genetic information is interpreted. This paper describes the conclusions of a consensus conference to address the use and interpretation of CF mutation analysis in clinical settings. Although the diagnosis of CF is usually straightforward, care needs to be exercised in the use and interpretation of genetic tests: genotype information is not the final arbiter of a clinical diagnosis of CF or CF transmembrane conductance regulator (CFTR) protein related disorders. The diagnosis of these conditions is primarily based on the clinical presentation, and is supported by evaluation of CFTR function (sweat testing, nasal potential difference) and genetic analysis. None of these features are sufficient on their own to make a diagnosis of CF or CFTR-related disorders. Broad genotype/phenotype associations are useful in epidemiological studies, but CFTR genotype does not accurately predict individual outcome. The use of CFTR genotype for prediction of prognosis in people with CF at the time of their diagnosis is not recommended. The importance of communication between clinicians and medical genetic laboratories is emphasized. The results of testing and their implications should be reported in a manner understandable to the clinicians caring for CF patients.
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| 2. |
- Gilljam, Marita, 1956, et al.
(author)
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Airway inflammation and infection in congenital bilateral absence of the vas deferens
- 2004
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In: Am J Respir Crit Care Med. ; 169:2
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Journal article (peer-reviewed)abstract
- In cystic fibrosis (CF), airway disease begins early in life. Bacteria and elevated levels of neutrophils and inflammatory mediators have been detected in bronchoalveolar lavage (BAL) fluid from infants with CF. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) are common in men with congenital bilateral absence of the vas deferens (CBAVD) and it has been suggested that this syndrome represents a mild form of CF. We hypothesized that men with CBAVD also have subclinical pulmonary disease. Bronchoscopy with BAL, viral and quantitative bacterial cultures, and analyses of total and differential cell count, cytokines, and free neutrophil elastase was performed in eight men with CBAVD, who had mutations in the CFTR and intermediate or elevated sweat chloride levels, and in four healthy control subjects. There was light growth of Staphylococcus aureus in one of eight men with CBAVD, and small numbers of opportunistic gram-negative bacteria in six of eight men with CBAVD and in one control subject. BAL cell counts and neutrophil elastase were within the normal range. Interleukin-8 and tumor necrosis factor-alpha levels were higher for men with CBAVD than for control subjects. These data suggest that mutations in the CFTR in men with CBAVD, in addition to causing infertility, lead to subclinical bacterial pulmonary infection and inflammation consistent with mild CF.
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| 3. |
- Gilljam, Marita, 1956, et al.
(author)
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Clinical Manifestations of Cystic Fibrosis Among Patients With Diagnosis in Adulthood
- 2004
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In: Chest. ; 126:4
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To define the clinical characteristics and diagnostic parameters of patients with cystic fibrosis (CF) diagnosed in adulthood. DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS AND METHODS: All patients with a diagnosis of CF made at the Toronto CF Clinics between 1960 and June 2001. Data were collected prospectively and analyzed retrospectively. RESULTS: There were 73 of 1,051 patients (7%) with CF diagnosed in adulthood. Over time, an increasing number and proportion of patients received a diagnosis in adulthood: 27 patients (3%) before 1990, compared to 46 patients (18%) after 1990 (p < 0.001). The mean sweat chloride level was lower for those with CF diagnosed as adults, compared to those with a diagnosis as children (75 +/- 26 mmol/L and 100 +/- 19 mmol/L, respectively; p < 0.001) [mean +/- SD], and adults were more likely to have pancreatic sufficiency (PS) than children (73% vs 13%, respectively; p < 0.0001). In 46 adults who received a diagnosis since 1990, the reason for the initial sweat test was pancreatitis (2 patients, 4%), pulmonary symptoms (18 patients, 39%), pulmonary and GI symptoms (10 patients, 22%), infertility (12 patients, 26%), and genetic screening (4 patients, 9%). Other manifestations were biliary cirrhosis (one patient) and diabetes mellitus (four patients, 9%). The diagnosis could be confirmed by sweat test alone in 30 of 46 patients (65%), by mutation analysis alone in 15 patients (33%), and by a combination in 31 patients (67%). Nasal potential difference (PD) measurements alone confirmed the diagnosis in the remaining 15 patients (33%). CONCLUSION: Patients with CF presenting in adulthood often have PS, inconclusive sweat test results, and a high prevalence of mutations that are not commonly seen in CF diagnosed in childhood. Although most patients have lung disease of variable degrees, single-organ manifestations such as congenital bilateral absence of the vas deferens and pancreatitis are seen. Repeated sweat tests and extensive mutation analysis are often required. Nasal PD may aid the diagnosis, but has not been standardized for clinical diagnosis.
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| 4. |
- Gilljam, Marita, 1956, et al.
(author)
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GI Complications After Lung Transplantation in Patients With Cystic Fibrosis
- 2003
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In: Chest. ; 123:1
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Journal article (peer-reviewed)abstract
- STUDY OBJECTIVE: Lung transplantation is now available for patients with cystic fibrosis (CF) and end-stage lung disease. While pulmonary graft function is often considered the major priority following transplantation, the nonpulmonary complications of this systemic disease also continue. We examined the GI complications in a cohort of patients who underwent transplantation. DESIGN: This was a retrospective study of all patients with CF who underwent transplantation between March 1988 and December 1998 in Toronto. Medical records were reviewed, and a short questionnaire was mailed to patients who were alive as of December 1998. RESULTS: There were 80 bilateral lung transplants performed in 75 patients. The questionnaire was distributed to 43 patients, of whom 27 patients (63%) responded. Pancreatic insufficiency requiring enzyme intake was evident in 72 of 75 patients (96%) at the time of surgery. Of three pancreatic-sufficient patients (4%), pancreatic insufficiency was diagnosed in two patients later. Biliary cirrhosis was diagnosed in three patients prior to transplantation. Distal intestinal obstruction syndrome (DIOS) was recorded for 15 patients (20%). Ten patients had a single episode, of which eight episodes occurred early in the postoperative period. Five patients had recurrent episodes. All were medically treated, except for two patients who underwent surgery. Other complications included cholecystitis (n = 3), mucocele of the appendix (n = 1), peptic ulcer disease (n = 3), and colonic carcinoma (n = 1). CONCLUSION: GI complications after lung transplantation are common in patients with CF, and attention should be paid to the risk for DIOS in the early postoperative period. Prevention and early medical treatment are important in order to avoid acute surgery. Close collaboration with the CF clinic, in order to diagnose and treat CF-related complications, is recommended.
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| 5. |
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| 6. |
- Klassen, Henry, et al.
(author)
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Neural precursors isolated from the developing cat brain show retinal integration following transplantation to the retina of the dystrophic cat
- 2007
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In: Veterinary Ophthalmology. - : Wiley. - 1463-5216 .- 1463-5224. ; 10:4, s. 245-253
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Journal article (peer-reviewed)abstract
- The cat has served as an important nonrodent research model for neurophysiology and retinal degenerative disease processes, yet very little is known about feline neural precursor cells. To culture these cells and evaluate marker expression, brains were dissected from 45-day-old fetuses, enzymatically dissociated, and grown in the presence of EGF, bFGF and PDGF. Expanded cells widely expressed nestin, Sox2, Ki-67, fusin (CXCR4) and vimentin, while subpopulations expressed A2B5, GFAP, or beta-III tubulin. Precursors prelabeled with BrdU and/or transduced with a recombinant lentivirus that expresses GFP were transplanted subretinally in five dystrophic Abyssinian cats. Two to 4 weeks following surgery, histology showed survival of grafted cells in three of the animals. Labeled cells were found in the neuroretina and RPE layer, as well as in the vitreous and the vicinity of Bruch's membrane. There was no evidence of an immunologic response in any of the eyes. Neural precursor cells can therefore be cultured from the developing cat brain and survive as allografts for up to 4 weeks without immune suppression. The feasibility of deriving and transplanting feline neural precursor cells, combined with the availability of the dystrophic Abyssinian cat, provide a new feline model system for the study of retinal repair.
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