Case-control study of acute renal failure in patients with cystic fibrosis in the UK.

BACKGROUND: There has been a recent increase in the number of reported cases of acute renal failure (ARF) in cystic fibrosis (CF). A case-control study was conducted to determine the factors which are associated with an increased risk of ARF. METHODS: 24 cases of confirmed ARF were identified in patients with CF from 20 UK CF centres presenting between 1997 and 2004. Using the UK CF database, sex- and age-matched controls were identified. Risk factors were analysed by conditional logistic regression and Mantel-Haenszel analysis. RESULTS: 21 of the 24 patients with ARF had received an aminoglycoside at the time of their episode of ARF or in the preceding week compared with only 3 of 42 controls during the same time period (OR 81.8, 95% CI 4.7 to 1427, p<0.001). In the year before the episode of ARF, significantly more cases than controls had received gentamicin (19/24 cases vs 1/42 controls, p<0.001). The numbers receiving tobramycin were similar (9/24 cases vs 16/42 controls, p = 0.9). A known risk factor for renal impairment (prior renal disease, acute dehydration or long-term treatment with a nephrotoxic drug) was present in 18/24 cases and 7/42 controls (OR 24.0, 95% CI 3.1 to 186.6, p = 0.002). CONCLUSIONS: In patients with CF the use of an intravenous aminoglycoside is a risk factor for ARF; gentamicin is more nephrotoxic than tobramycin. Most patients who develop ARF have a risk factor which necessitates withholding aminoglycosides or more closely monitoring their use.

Pulmonary infection in mild variant cystic fibrosis: implications for care.

BACKGROUND: Disease phenotype in cystic fibrosis (CF) shows considerable heterogeneity. Atypical or mild mutations in the CFTR gene have been linked to late-onset pulmonary disease; however, few reports document the condition of the airway in infants and young children with apparent "mild" disease. Prognosis is uncertain in this group of patients and this, in turn, has led to inconsistency in management. Our initial experience of pulmonary infection in children with mild variant CF prompted a more detailed review of clinical outcome. METHODS: A retrospective cohort study was carried out comparing frequency of bacterial isolates and clinical outcomes in eleven compound heterozygotes for DeltaF508 and a second mild mutation, mainly R117H, with a matched group of DeltaF508 homozygotes. RESULTS: Staphylococcus aureus was isolated in 8 of the 11 patients with mild variant disease and Pseudomonas aeruginosa found in 7 (64%), although the frequency of positive cultures was significantly less (2.8/year) than the DeltaF508 homozygotes (6.1/year, p<0.05). Shwachman scores (median+range) were significantly higher in patients with mild mutations - 94, 74-92 vs. 88, 77-91; p<0.005); there was also a small but significant difference in chest radiograph (Chrispin-Norman) scores (median+range) (mild 5.1, 4-9, vs. severe 5.8, 3-10; p 0.04). There was little difference in lung function in terms of FEV1 (median+range) between the two groups (% predicted, mild 86.5, 68-87 vs. severe 76.0, 65-88; p 0.5). CONCLUSIONS: Most patients with mild variant CF will have bacterial isolates from airway cultures requiring antibiotic therapy three to four times a year. Infection with both S. aureus and P. aeruginosa is common. Anti-staphylococcal prophylaxis for the first two years should be considered.

Pubertal growth and development in cystic fibrosis: a retrospective review.

AIM: Normal growth patterns are seen throughout the first decade in children with cystic fibrosis (CF). Growth in the second decade is, however, less satisfactory and may reflect pubertal delay. This study was performed to assess the extent of pubertal delay, to examine factors that influence the timing and magnitude of the pubertal growth spurt, and to establish whether the final height for most CF patients differed significantly from the normal population. METHODS: Thirty subjects (16 male) attending a single centre were studied. Peak height velocity (PHV), final height and ages when achieved were compared with population norms. Outcome data were correlated with disease severity using Shwachman and Chrispin-Norman scores and forced expiratory volume in 1 s. RESULTS: PHV was significantly later in both genders in this CF population compared with Tanner and Whitehouse standards: boys 14.6 y (95% confidence interval (95% CI) 12.4-16.8, p < 0.01) and girls 12.6 y (95% CI 10.5-14.7, p < 0.01). Mean PHV was also lower in both genders (boys 7.7 cm y(-1) and girls 6.4 cm y(-1), both p<0.001). However, final heights did not differ significantly from Freeman standards (height standard deviation scores: males--1.2, females--0.1); 52% of final heights equalled or exceeded the mid-parental centile. CONCLUSION: CF patients showed suboptimal PHVs with a later pubertal growth spurt influenced by disease severity, but eventually achieved a normal final height.

Pilot safety study of liposomal prostaglandin (PGE1) in respiratory exacerbations in cystic fibrosis.

BACKGROUND: A pilot evaluation to assess the safety and possible benefits of TLC C-53, (prostaglandin E(1) associated with egg phosphatidylcholine liposomes) in acute respiratory exacerbations in children with cystic fibrosis (CF). METHODS: Randomised, double-blind, placebo-controlled study in 20 P. aeruginosa colonised patients. All received intravenous antibiotics. Subjects were given a rising dose of TLC C-53 (0.15-1.8 microg/kg) by 4 x 1-h infusions. Primary outcome measures were sputum IL-6, IL-8 and sputum neutrophil elastase. The rate of decline in lung function was determined at 6 weeks post-therapy as was the interval until the next respiratory exacerbation requiring intravenous antibiotic therapy. RESULTS: Analysis of primary and secondary outcome measures failed to show any significant differences between the two groups, although trends favoured the treated group. Decline in lung function over 6 weeks favoured the TLC C-53 group (FEV(1) mean difference 4.3%, 95% CI=-6.8, 15.4%). Time to next exacerbation also favoured the TLC C-53 group with a mean time to exacerbation for TLC C-53 of 26.0 weeks against 11.9 weeks. CONCLUSIONS: A larger multi-centre trial of TLC C-53 as an adjunct to antibiotic therapy in respiratory exacerbations in CF would appear warranted.

Determining preferred educational methods for neurological surgery residents regarding organ donation.

Design and implementation of professional education, especially physician education, continues to challenge procurement professionals. At the request of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons, the United Network for Organ Sharing undertook a project to develop educational materials for neurological surgery residents. A survey tool was developed and administered on site at 11 neurological surgery residency programs in the United States. The survey explored the types of learning environments, teaching methods, educational resources, and audiovisual aids that neurological surgery residents typically experience during their residency programs. In addition, the survey sought to uncover the residents' informational needs regarding organ and tissue donation presentations as well as their educational program preferences. Based on our findings, neurological surgery residents prefer presentations that are brief and to the point, that are easily understood, that require no reading, that contain limited important information, and that always include food.

The coordinator attrition problem in the United States: myth or reality?

Excessive attrition among organ procurement coordinators has been suspected problem for many years. In 1994 the United Network for Organ Sharing undertook a procurement coordinator attrition study. Initially, focus groups were conducted in conjunction with the 1994 North American Transplant Coordinators Organization's annual meeting. In 1996, 69 executive directors from organ procurement organizations were surveyed on the subject of procurement coordinator attrition. Thirty-five executive directors responded, resulting in a 51% response rate. The UNOS procurement coordinator attrition study explored actual attrition rates, relationships of certain demographic factors to attrition rates, economic impact of attrition on the organizations, and various job tenure issues. The period under study was January 1, 1990 through December 31, 1993. Results did not demonstrate an industry-wide attrition problem. Additionally, the study revealed no enduring attrition problem in any single organization, and some organizations were found to have no attrition during the entire study period.

Immunogenicity and tolerability of a trivalent influenza subunit vaccine (Influvac) in high-risk children aged 6 months to 4 years.

Fifty-two children, aged less than 5 years, with chronic lung disease or congenital heart disease were entered into a two-centre open study to determine the immunogenicity and tolerability of Influvac, a trivalent influenza sub-unit vaccine. Seroresponses were determined following two intramuscular vaccinations with 0.25 ml of Influvac, four weeks apart. Any local or systemic reaction was sought. Seroresponses were age and antigen specific, with children older than 9 months showing better seroresponses to all three antigens. Both A/Taiwan and B/Panama strains met all efficacy criteria. A/Shangdong met two of the three criteria: seroconversion and mean geometric titre increase. Local (23%) and systemic (48%) reactions following either of the two vaccinations were minor in nature and resolved within a few days. The vaccine induced a strong antibody response against all three haemagglutinin antigens and was well tolerated. The incidence of local and systemic reactions was comparable with those reported in healthy adults.

Modification of nasal membrane potential difference with inhaled amiloride and loperamide in the cystic fibrosis (CF) mouse.

BACKGROUND: In the airway of subjects with cystic fibrosis (CF) the combination of defective cAMP mediated chloride secretion and enhanced sodium absorption leads to dehydration of mucosal mucus and is reflected in an increased trans-epithelial potential difference (PD). The airway secretions may be less viscid and easier to expectorate if sodium (and water) reabsorption is inhibited. METHODS: To evaluate the response to sodium blocking agents, changes in the nasal PD in 20 transgenic CF mice were compared with 14 control mice (MF1 strain) before and after administration of nebulised amiloride and loperamide (both in a concentration of 1 mmol/l). The duration of action for both drugs was also determined after a single inhaled dose of 1 mmol/l for two minutes. RESULTS: The median basal PD was -24 mV in controls and -28 mV in CF mice (p < 0.01). This fell in CF mice after amiloride and loperamide administration by 15 mV and 14 mV, respectively, compared with a decrease of 7 mV and 5.5 mV in controls (p < 0.01). There was no further change in PD when loperamide was given after amiloride. This suggests that loperamide and amiloride may act on sodium absorption via similar mechanisms. Loperamide had a longer duration of action after a single administration than amiloride. CONCLUSION: The administration of amiloride and loperamide reduces the transepithelial potential and inhibits sodium reabsorption in the CF mouse airway. Further studies are required to determine if the more prolonged action of loperamide could be of therapeutic use.

Head growth in cystic fibrosis following early diagnosis by neonatal screening.

Growth in length, weight gain, and head circumference were recorded from 3 months to 4 years of age in 25 children with cystic fibrosis diagnosed by neonatal screening. Mean standard deviation (SD) scores at 3 months for length, weight, and head circumference were -0.78, -0.91, and -0.52 respectively. Over the first 2 years length SD scores showed a consistent improvement and stabilised at 0.1 SD below mean from 2 to 4 years. Weight SD scores remained essentially unaltered throughout, approximately 1 SD below the mean. Head circumference, however, after an initial increase from -0.52 at 3 months to -0.25 at 18 months, slowed and fell to 1 SD below the mean at 4 years. The data suggest that head growth continues to lag behind somatic growth in children with cystic fibrosis despite early diagnosis and good nutritional management in early infancy. These data also support functional expression of cystic fibrosis transmembrane conductance regulator in the brain.

Disproportionate head growth retardation in cystic fibrosis.

Monthly increments of length, weight gain, and head circumference were recorded from birth to 4 years of age in 52 children with cystic fibrosis. At birth the children showed stunting. Standard deviation (SD) scores at birth for height, weight, and head circumference were -1.24, -0.72, and -1.82 respectively. Over the first four years, length and weight SD scores showed a consistent improvement. However, there was very limited improvement in head circumference, which stabilised 1 SD below the mean from 1.5 years to 4 years. Our data suggest that head growth lags behind gain in height and weight in children with cystic fibrosis despite good nutritional management in early infancy. The data may also support the expression of cystic fibrosis transmembrane conductance regulator in choroid plexus and ependyma.

Bacterial reservoirs in cystic fibrosis.

To establish whether colonisation of the upper respiratory tract or bacterial contamination of inhaler devices or solutions predisposes to colonisation of the lower respiratory tract in patients with cystic fibrosis, bacterial isolates from groups of children who were positive (n = 13) or negative (n = 18) for Pseudomonas aeruginosa were studied. Cultures of swabs from inhaler devices, toothbrushes, and upper airways were compared with cough swabs or sputum cultures. No pathogens were obtained from inhaler equipment administering unit dose medications. Upper airway carriage of Staphylococcus aureus and Haemophilus influenzae was identified in both groups but correlated poorly with sputum isolates. P. aeruginosa was found only in the upper respiratory tract of children with established colonisation of the lower airways. No P aeruginosa isolates were obtained from the upper airways of the group with negative sputum, including one patient who became colonised by P aeruginosa during the study. Our results did not support the suggestion that colonisation of the upper respiratory tract by P aeruginosa predisposes to colonisation of the lower airways. Failure to isolate pathogenic organisms consistently from the upper airways in patients with positive sputum argues against a local epithelial factor predisposing to bacterial colonisation.

Detection of cow's milk protein intolerance by an enzyme-linked immunosorbent assay.

Circulating IgG antibodies to cow's milk proteins have been quantified in 182 children using an enzyme-linked immunosorbent assay (ELISA). Antibody levels in children with cow's milk protein intolerance (CMPI) were compared with those in control groups comprising other diarrhoeal diseases, atopic children, and a "normal" sample including children with toddler diarrhoea. Mean IgG antibody levels in children with CMPI were significantly higher than in any of the control groups. There were clear differences in peak antibody levels between CMPI and all other groups for each of the protein fractions tested. There was some overlap in titres between CMPI and other enteropathies but the assay gave 88% sensitivity and specificity for the diagnosis of CMPI overall and was 100% specific against the combination of non-enteropathic controls in this study. These findings indicate that the assay could be applied as an outpatient screening test for CMPI and would be particularly useful in differentiating "toddler" diarrhoea from CMPI.

The use of fluff counts in a study of hygiene in Queensland hatcheries.

During 1972, 333 fluff samples were tested from 13 Queensland hatcheries and assessed according to the English standards for total count, coliforms and fungi. They were also assessed as being "standard" or "substandard", using a combination of the criteria of the English system. All hatcheries had at least 2 substandard samples and all the samples from 2 hatcheries were substandard.