Ethoxycoumarin O-deethylation (ECOD) activity in rat liver slices exposed to beta-naphthoflavone (BNF) in vitro

1. To test whether cystic fibrosis (CF) altered the kinetics and dynamics of oral salbutamol, 11 patients with CF (19-33 years old; five females; FEV1: 37 +/- 12% of predicted value) and 10 healthy volunteers (20-41 years old; five females; FEV1: 99 +/- 14% of predicted value) received orally 4 mg salbutamol. 2. The estimated pharmacokinetic parameters of salbutamol in patients with CF were identical to those in healthy subjects. For instance, peak plasma concentrations of salbutamol were 10.5 +/- 2.6 (mean +/- s.d.) and 10.2 +/- 2.9 ng ml-1 (NS), and the area under salbutamol plasma concentrations as a function of time (AUC (0, 7 h)) was 43.0 +/- 9.3 ng ml-1 h and 43.3 +/- 12.7 ng ml-1 h (NS) in CF patients and in healthy subjects, respectively. Since on a mg kg-1 dose basis, CF patients received a dose 28% greater than healthy subjects, this lack of differences implies a decrease in the amount of salbutamol absorbed, or alternatively, an increase in both clearance and volume of distribution of salbutamol. 3. Salbutamol did not elicit bronchodilation in CF patients, but increased heart rate from 77 +/- 2 to 103 +/- 3 beats min-1 (P < 0.05). 4. Salbutamol decreased plasma potassium concentrations from 4.5 +/- 0.1 to 3.8 +/- 0.1 mmol l-1 in the CF group (P < 0.05) and from 4.1 +/- 0.2 to 3.4 +/- 0.1 mmol l-1 in the controls (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of flutter and PEP mask physiotherapy on symptoms and lung function in children with cystic fibrosis

Recently, the flutter was introduced as a new device to improve sputum expectoration. Preliminary data suggested a significant improvement in expectoration and lung function during flutter treatment in patients with cystic fibrosis (CF). The aim of the present study was to compare the effects of the flutter and the positive expiratory pressure (PEP) mask on symptoms and lung function in children with CF. In a crossover randomized study 22 patients with CF (mean age 12 yrs, range 7-17 yrs) performed physiotherapy using either the flutter or the PEP mask twice a day during two treatment periods of 2 weeks, separated by a one week wash-out period, in a random sequence. Lung function parameters (peak expiratory flow, forced vital capacity (FVC), forced expiratory volume in one second, maximal midexpiratory flow, maximal expiratory flow at 25% of FVC, thoracic gas volume, total lung capacity, residual volume/total lung capacity, airway resistance and specific airway conductance) and changes in transcutaneous oxygen haemoglobin saturation were assessed before and after the first supervised session and at the end of each treatment period. Throughout the study peak flow was measured and symptoms were scored daily. No significant changes in any lung function parameter occurred after a single session or after 2 weeks of physiotherapy with either method. There was no difference in acceptability and subjective efficacy. In conclusion, any superiority of the flutter over the positive expiratory pressure mask technique for expectoration could not be confirmed during 2 weeks of daily treatment in children with cystic fibrosis. Both methods are well accepted by children and do not change lung function. Long-term comparison of both methods, including expectoration measurements, seems to be required for further evaluation of the potential success of physiotherapy in cystic fibrosis.     

Holding the baby: head downwards positioning for physiotherapy does not cause gastro-oesophageal reflux

The head-downwards tipped position for physiotherapy has been claimed to exacerbate gastro-oesophageal reflux (GOR) in infants with cystic fibrosis (CF). This was investigated using lower oesophageal pH monitoring during physiotherapy. Twenty-one infants (age range 1-27 months) with respiratory disorders (CF=11), undergoing lower oesophageal pH monitoring were recruited. Subjects received two physiotherapy episodes in random order, A/B or B/A, 12 h apart. A began the gravity-assisted positioning head downward tip for: right lower lobe, middle lobe, left lower lobe and lingula; then supine with no tip for anterior segments of the upper lobes followed by apical segments of upper lobes in a sitting position. B was in the reverse order. Intermittent chest clapping was carried out for 4 min in each position by a physiotherapist blinded to the pH data. During episode A, the median change in pH from baseline was -0.32 (range -2.07 to +1.0) in non-CF subjects (NS) and -0.52 (range -2.7 to +0.52) in CF subjects (p<0.02). During episode B, the median change in non-CF subjects was -0.1 (NS; range - 1.7 to -0.15) and in CF subjects was -0.05 (NS; range -0.67 to +0.5). There was no order effect for positioning. In the CF subjects the sitting position was twice as likely to have the lowest pH measurement during physiotherapy than the other positions (p<0.04). In conclusion, the head-downward tipped positioning for physiotherapy treatment neither induces nor aggravates gastro-oesophageal reflux. There is no justification for routinely changing the way in which infant physiotherapy is carried out.     

Elevation of antibodies to cytomegalovirus and other herpes viruses in pulmonary fibrosis

The aim of this study was to determine whether latent viral infection is associated with idiopathic pulmonary fibrosis (IPF), an interstitial lung disease whose aetiology remains to be elucidated. Cytomegalovirus (CMV) immunoglobulin G (IgG) and complement fixation (CF), Epstein-Barr (EB) viral capsid antigen (VCA) IgG, herpes simplex virus (HSV) IgG, adenovirus CF, and parainfluenza 3 virus haemagglutinin inhibition (HI) titres were measured in the serum from patients with pulmonary diseases. The study included five subject groups: 35 normal controls (aged (mean +/- SD) 38 +/- 17 yrs); 43 IPF (63 +/- 10 yrs), seven collagen vascular disease-related interstitial pneumonitis (CVD-IP) (62 +/- 12 yrs); 22 sarcoidosis (36 +/- 14 yrs); and 17 emphysema (66 +/- 11 yrs). Levels of CMV IgG in IPF (87.6 +/- 51.7) and CVD-IP (101.2 +/- 69.9) were significantly elevated compared to those in the control (30.9 +/- 24.1), sarcoidosis (34.4 +/- 38.3) and emphysema groups (40.3 +/- 24.6), whereas CMV immunoglobulin M (IgM) was generally below the limit of detection. Similarly, CMV CF titres in IPF and CVD-IP were elevated compared to those in other diseases. EB VCA IgG titres in IPF, CVD-IP and emphysema and HSV IgG in IPF were also elevated. In contrast, adenovirus CF and parainfluenza 3 HI titres demonstrated no significant difference among all of the groups investigated. Increases in cytomegalovirus immunoglobulin G and complement fixation titres with negative cytomegalovirus immunoglobulin M suggest that latent cytomegalovirus infection may be more prominent in idiopathic pulmonary fibrosis or collagen vascular disease-related interstitial pneumonitis. Together with the elevation of Epstein-Barr virus viral capsid antigen and herpes simplex virus immunoglobulin G in idiopathic pulmonary fibrosis and/or collagen vascular disease-related interstitial pneumonitis, it is rational to assume that these viruses may be implicated in the development of pulmonary fibrosis. Further study is necessary to investigate the relationship between latent viral infection and pulmonary fibrosis.     

Circulating transferrin receptor assay--coming of age

Gastro-oesophageal reflux (GOR) occurs frequently in children with cystic fibrosis (CF) but has not been studied in adult CF. We surveyed such symptoms by structured questionnaire in 50 adult CF patients (mean age 26 years, range 16-50; 24 male) and performed oesophageal manometry and 24-hour pH recording in 10 who had reflux symptoms (mean age 28 years, range 21-35; 8 men). 47 patients (94%) had upper gastrointestinal symptoms: 40 (80%) heartburn (27 worse when supine); 26 (52%) regurgitation; and 28 (56%) dyspepsia. At oesophageal manometry, lower oesophageal sphincter barrier pressure (LOSBP) was subnormal in 6 of the 10 patients and 3 had uncoordinated peristalsis in the mid oesophagus. 8 patients had raised DeMeester scores, indicating significant GOR. Those patients with a LOSBP < 5mm Hg had a higher DeMeester score (mean 81.0, range 47.9-128.8) than the patients with a normal LOSBP (26.9, 8.7-56.5; p < 0.002). These results show that adult CF patients have high rates of GOR symptoms, diminished LOSBP, and acid reflux.     

In vivo measurement of chloride and water secretion in the jejunum of cystic fibrosis patients

In the present study, we have investigated the possible consequences of the chloride channel defect in the intestine of cystic fibrosis (CF) patients for electrolyte and water transport in the jejunum in vivo, using a multilumen, double occluding balloon catheter, and an Ag/AgCl intraluminal electrode. During a chloride-free perfusion, to optimize the sensitivity of our measurements, the transmural potential difference (PD) (lumen with reference to serosal side) was found to be significantly higher in the jejunum of CF patients (+8.0 +/- 2.1 mV; n = 5) than in healthy control subjects (-2.2 +/- 2.0 mV; n = 9). The chloride concentration measured in chloride-free jejunal perfusates of CF patients was significantly lower than in controls (10.9 +/- 2.3 and 41.4 +/- 8.2 mM, respectively). Possible differences in net chloride and water secretion did not reach statistical significance (chloride secretion controls: -2.1 +/- 0.9 mmol/10 cm/h; CF: -0.8 +/- 0.2 mmol/10 cm/h; water secretion controls: -0.8 +/- 2.5 mL/10 cm/h; CF: -11.7 +/- 8.9 mL/10 cm/h). In control subjects, intraluminally applied theophylline stimulated the secretion of water (delta 23.4 +/- 4.6 mL/10 cm/h) and chloride (delta 4.1 +/- 1.1 mmol/10 cm/h), but not in CF patients (respectively delta 3.6 +/- 3.3 mL/10 cm/h and delta 1.1 +/- 1.1 mmol/10 cm/h). In controls, theophylline caused a significant increase in lumen negativity (PD -10.2 +/- 2.6 mV), but no change could be seen in CF patient transmural PD. These observations provide in vivo evidence for a decreased chloride permeability in the jejunum in CF, resulting in a significant reduction in net electrolyte and water secretion in the presence, but not in the absence, of an intestinal secretagogue.     

Conflict in families of adolescents: The impact on cohesion and power structures.

Investigated 3 characteristics (locus, content, and frequency) of conflict (CF) in families of adolescents. Ss were 134 parents and 170 early (mean age 11.5 yrs), 109 middle (mean age 16.3 yrs), and 47 late (mean age 18.7 yrs) adolescents. Ss reported family CF on T. M. Gehring and S. S. Feldman's (see record 1989-14119-001) Family System Test and in an interview. CF in marital (MADs) and parent–adolescent dyads (PADs) was frequently reported. Across adolescence, reports of PAD CF increased, especially those related to autonomy. CF decreased cohesion and changed power relations in the representations of family structure. CF in the MAD was related to decreased cohesion and increased cross-generational coalitions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Discriminative stimulus effects of S(-)-methcathinone (CAT): a potent stimulant drug of abuse

Elevated circulating plasma nonesterified fatty acids (NEFA) may contribute to the insulin resistance and hyperglycemia of non-insulin-dependent diabetes mellitus (NIDDM), and decreasing plasma NEFA could provide a therapeutic benefit. A sustained-release preparation of acipimox, a lipolysis inhibitor, was used in an attempt to decrease circulating plasma NEFA levels long-term, and the effects on glycemic control, insulin resistance, and serum lipids were measured. Sixty NIDDM patients (43 males and 17 females) took part in a randomized controlled trial of acipimox or placebo for 12 weeks. Fasting plasma NEFA levels did not change in acipimox-treated patients (baseline v 12 weeks, 0.84 +/- 0.35 v 0.88 +/- 0.55 mmol x L(-1), mean +/- SD). Fasting blood glucose was unchanged (mean difference v placebo, -0.5 mmol x L(-1); 95% confidence interval [CI], -1.4 to 0.3 mmol x L[-1]), but serum fructosamine decreased (mean difference v placebo, -26 micromol x L(-1); 95% CI, -51 to 0 mmol x L[-1]), as did the standardized hemoglobin A1 ([HbA1] mean difference v placebo, -1.4%; 95% CI, -3.0% to -0.1%). Insulin resistance measured as steady-state plasma glucose during an insulin-dextrose infusion test was unchanged (mean difference v placebo, -1.4 mmol x L(-1); 95% CI, -3.2 to 0.5 mmol x L[-1]). Serum total cholesterol (mean difference v placebo, -0.4 mmol x L(-1); 95% CI, -0.6 to -0.1 mmol x L[-1]), serum apolipoprotein B ([apo B] mean difference v placebo, -0.19 g x L(-1); 95% CI, -0.3 to -0.1 g x L[-1]), and serum triglycerides (mean difference v placebo for pretreatment v posttreatment ratio, 0.59; 95% CI, 0.40 to 0.88) were all lower with acipimox. Serum high-density lipoprotein (HDL) cholesterol (mean difference v placebo, 0.10 mmol x L(-1); 95% CI, -0.05 to 0.3 mmol x L[-1]), serum apo A1 (mean difference v placebo, 0.03 g x L(-1); 95% CI, -0.04 to 0.1 g x L[-1]), and serum lipoprotein(a) ([Lp(a)] acipimox v placebo, 154 (0 to 1,574) v 71 (0 to 1,009), median and range) were unchanged. Despite the lack of change in fasting plasma NEFA levels, acipimox caused a modest beneficial improvement in overall glycemic control and plasma lipids in NIDDM patients and could be a useful agent in the treatment of dyslipidemic NIDDM patients.     

Predicting medical compliance among adolescents with cystic fibrosis.

Developed an incomplete stories assessment tool based on a competency/coping skills model in predicting medical compliance of adolescents with cystic fibrosis (CF). Data from 40 CF patients (aged 13–23 yrs) were compared to objective measures of each S's medical compliance. Results show that the test was positively correlated with compliance and discriminated compliant from noncompliant Ss. It is suggested that data derived from Ss' responses could be used projectively to provide information useful to clinicians treating adolescents with CF. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Occupational Health Research in Developing Countries: The Experience in Ecuador

We report the results of a double-blind, placebo-controlled trial in nine cystic fibrosis (CF) subjects receiving cationic liposome complexed with a complementary DNA encoding the CF transmembrane conductance regulator (CFTR), and six CF subjects receiving only liposome to the nasal epithelium. No adverse clinical effects were seen and nasal biopsies showed no histological or immuno-histological changes. A partial restoration of the deficit between CF and non-CF subjects of 20% was seen for the response to low Cl- perfusion following CFTR cDNA administration. This was maximal around day three and had reverted to pretreatment values by day seven. In some cases the response to low Cl- was within the range for non-CF subjects. Plasmid DNA and transgene-derived RNA were detected in the majority of treated subjects. Although these data are encouraging, it is likely that transfection efficiency and the duration of expression will need to be increased for therapeutic benefit.     

Blood pressure changes during short-term fluoxetine treatment

PURPOSE: To evaluate the potential diagnostic role of mediastinal sonography in patients with cystic fibrosis (CF), we screened the mediastinum of adult CF patients with and without signs of infection and healthy controls. METHODS: Fifty-four consecutive adult patients with CF and 53 healthy volunteers underwent high-resolution mediastinal sonography. The paratracheal region and aorticopulmonary window of each subject were examined for lymph nodes. Each patient was screened for clinical signs of infection. RESULTS: Lymph nodes were detectable in the mediastinum of 39 of 50 CF patients (78%); the mean total lymph node volume was 1.5 +/- 1.7 cm3. Lymph nodes were detectable in the mediastinum of 31 of 50 controls (62%); the mean total lymph node volume in this group was 0.3 +/- 0.3 cm3 (p < 0.001). In the 30 CF patients with signs of infection, the mean total lymph node volume was larger (2.0 +/- 1.8 cm3) than in the 20 CF patients without signs of infection (0.7 +/- 0.9 cm3; p = 0.002). CONCLUSIONS: These results indicate that lymph node volume determination by high-resolution mediastinal sonography may help assess inflammatory activity in patients with CF.     

Primary fallopian tube carcinoma. Report of a single case with review of the literature

The mean survival rates of female BDF1 mice transplanted intravenously (i.v.) with murine L1210 leukemia cells were significantly prolonged by intraperitoneal (i.p.) pretreatment (before i.v. transplantation) or by i.p. pre- and post-treatment (before and after the i.v. transplantation) with heat-killed Actinobacillus suis cells ATCC 15557 (AS 15557) alone, as compared with untreated L1210-leukemia-cell-bearing control mice. However, significant prolongation of the mean survival rates was not elicited by the i.p. post-treatment with AS 15557 alone. When 5-fluorouracil (5-FU) was applied i.p. to mice receiving post-treatment with AS 15557 alone, the mean survival rates of the L1210-leukemia-cell-bearing mice were significantly prolonged. The antileukemic action of AS 15557, alone or in combination with 5-FU, against L1210 leukemia was superior to that of a streptococcal preparation (OK-432) and was almost the same as of bacillus Calmette-Guérin with or without 5-FU. The results suggest the possibility that the synergism of AS 15557 in combination with 5-FU may be dependent on the relationship between the indirect immunological function of AS 15557 and the direct cytotoxic action of 5-FU on L1210 leukemia cells.     

Stomach motility and lyspafen

The effects of spermidine and spermine at varying concentrations upon the replicative ability of human fibroblasts in cell culture have been studied. The average concentrations of spermidine causing a 50% inhibition of prolifertion (ID50) after 3 days of growth for three normal cell strains and three strains derived from patients with cystic fibrosis (CF) were 4.4 X 10(-6) +/- 1.2 M and 6.2 X 10(-6) +/- 2.1 M, respectively. The values for spermine were 2.0 X 10(-6) +/- 0.5 M for normal and 2.2 X 10(-6) +/- 0.1 M for fibroblasts from cystic fibrosis patients. No significant difference between the replicative ability of normal and CF cell strains was seen over a wide range of polyamine concentrations employed for a period of up to 3 days.     

Transvaginal salpingoscopy: an office procedure for infertility investigation

In patients with cystic fibrosis (CF), nasal intermittent positive pressure ventilation (NIPPV) is currently used as a short-term bridge to transplantation but its precise role has yet to be determined. Patients were offered a therapeutic trial of NIPPV when candidates for lung transplantation, with respiratory failure unresponsive to medical treatment. Twelve patients, six male of mean age of 26 +/- 1.4 years, had a trial of NIPPV. At recruitment the mean percentage predicted forced expired volume in one second (FEV1) was 15.1% +/- 1.2%, arterial carbon dioxide (PaCO2) 8.7 +/- 0.6 kPa, arterial oxygen (PaO2) with variable FiO2 7.4 +/- 0.6 kPa and arterial bicarbonate (HCO3-) 40.1 +/- 1.6 mmol l-1. Ten cases tolerated NIPPV for 1-15 months, mean 5.1 +/- 1.4 months, with subjective improvement in headache and quality of sleep. At 3 months, there was significant improvement in forced vital capacity, PaCO2 and arterial HCO3- and there was a reduction in the number of hospital inpatient days (P < 0.05). Subsequently three cases had lung transplantation, four died on the active list and three are awaiting organs. Two patients failed to tolerate NIPPV owing to abdominal bloating and increasing hypercapnia. In conclusion, NIPPV, if tolerated, was a useful adjunct in the treatment of CF patients with hypercapnic respiratory failure awaiting transplantation. Further prospective studies are required to determine the optimum time to commence NIPPV and to clarify its precise role.     

Vitamin A deficiency and nocturnal vision in teenagers with cystic fibrosis

The aim of this study was to document plasma retinol status and nocturnal vision in ten eutrophic adolescents with cystic fibrosis (CF) receiving daily retinol supplementation. Plasma retinol, alpha and beta carotenes and retinol binding protein were measured in ten clinically stable CF patients (mean age: 14.3 years; Shwachman score: 80-100). Nocturnal vision evaluation was performed with a Beyne optometer. Plasma retinol (mean 0.42 +/- 0.16 mg/l), alpha carotene and beta carotene levels were below the lower limit of normal in all but one patient. Five out of ten patients with normal standard opthalmological examination presented a poor (n = 3 patients) or a pathological (n = 2) dark adaptation test. These two patients showed a dramatic increase in nocturnal vision after 1 year of adapted retinol supplementation. CONCLUSION: Low vitamin A levels occur frequently in clinically stable, eutrophic and retinol supplemented CF adolescents. Since vitamin A deficiency is associated with poor nocturnal vision and since this pattern can be reversed by adapted retinol supplementation, we recommend monitoring plasma vitamin A levels in CF patients and evaluation of dark adaptation in retinol deficient patients.     

Mucociliary clearance in cystic fibrosis knockout mice infected with Pseudomonas aeruginosa

In this study, we examined whether mucociliary clearance differed between cystic fibrosis (CF) knockout mice and wildtype controls. Additionally, we investigated whether infection with Pseudomonas aeruginosa, a common pathogen in the CF lung, affected this important host defence mechanism. Ciliary beat frequency (fcb) and particle transport (PT) were recorded using an in vitro lung explant preparation. Measurements were made from uninfected cystic fibrosis transmembrane conductance regulator (CFTR) knockout (-/-) mice and littermate controls (+/+) and compared to measurements from infected animals. While there were no differences detectable in fcb between CFTR -/- mice and their +/+ controls either in the presence or absence of P. aeruginosa, PT rates were different between these groups; interestingly, PT rates appeared dependent on both CFTR and infection status, with uninfected CFTR +/+ animals demonstrating higher rates of PT than their -/- littermates, while CFTR +/+ P. aeruginosa-infected mice demonstrated lower PT than knockout mice. These data demonstrate differences in mucociliary clearance between cystic fibrosis transmembrane conductance regulator knockout mice and controls, and further that Pseudomonas aeruginosa infection affects mucociliary clearance in the peripheral airways of mice. Additionally, the observed differences in particle transport suggest that cystic fibrosis transmembrane conductance regulator knockout mice demonstrate different mucociliary responses to infection.     

Early transition to oral antibiotic therapy for community-acquired pneumonia: duration of therapy, clinical outcomes, and cost analysis

Our objective was to compare therapeutic outcome and analyse cost-benefit of a 'conventional' (7-day course of i.v. antibiotic therapy) vs. an abbreviated (2-day i.v. antibiotic course followed by 'switch' to oral antibiotics) therapy for in-patients with community-acquired pneumonia (CAP). We used a multicenter prospective, randomized, parallel group with a 28 day follow-up, at the University-based teaching hospitals: The Medical Center of Louisiana in New Orleans, LA and hospitals listed in the acknowledgement. Ninety-five patients were randomized to receive either a 'conventional' course of intravenous antibiotic therapy with cefamandole 1 g i.v. every 6 h for 7 days (n = 37), or an abbreviated course of intravenous therapy with cefamandole (1 g i.v. every 6 h for 2 days) followed by oral therapy with cefaclor (500 mg every 8 h for 5 days). No difference was found in the clinical courses, cure rates, survival or the resolution of the chest radiograph abnormalities among the two groups. The mean duration of therapy (6.88 days for the conventional group compared to 7-30 days for the early oral therapy group) and the frequencies of overall symptomatic improvement (97% vs. 95%, respectively) were similar in both groups. Patients who received early oral therapy had shorter hospital stays (7.3 vs. 9.71 days, P = 0.01), and a lower total cost of care ($2953 vs. $5002, P < 0.05). It was concluded that early transition to an oral antibiotic after an abbreviated course of intravenous therapy in CAP is substantially less expensive and has comparable efficacy to conventional intravenous therapy. Altering physicians' customary management of hospitalized patients with CAP can reduce costs with no appreciable additional risk of adverse patient outcome.     

Glycolate kinetics and hemodialysis clearance in ethylene glycol poisoning. META Study Group

OBJECTIVE: Toxic manifestations following ethylene glycol exposure are due to accumulation of metabolites, particularly glycolate. We characterized glycolate elimination kinetics and dialysis properties in a series of ethylene glycol poisonings. METHODS: Patients who ingested ethylene glycol and received fomepizole (4-methylpyrazole; 4-MP) +/- hemodialysis were prospectively evaluated. Serial blood samples for ethylene glycol, glycolate, pH, and bicarbonate were drawn to determine glycolate elimination rate, t1/2, and correlations between initial glycolate and initial markers of acidosis. Dialyzer inlet and outlet samples were obtained to measure hemodialysis glycolate clearance. Plasma ethylene glycol and glycolate were determined by gas chromatography. RESULTS: Ten patients, mean age 49 years (range 28-73 years), presented a mean of 10.5 hours (range 3.5-21.5 hours) after ethylene glycol ingestion. Mean initial ethylene glycol was 18.5 mmol/L (range 0.8-62.2 mmol/L) (115 mg/dL; range 5-386 mg/dL) and glycolate was 17.0 mmol/L (range 10.0-23.7 mmol/L). Nine of 10 underwent hemodialysis. Nonhemodialysis (n = 4) elimination rate was 1.08 +/- 0.67 mmol/L/h (mean +/- SD) and t1/2 was 626 +/- 474 minutes. Elimination t1/2 during hemodialysis (n = 8) was 155 +/- 42 minutes. Hemodialysis clearance (n = 5) was 170 +/- 23 mL/min with flow rates 250-400 mL/min. Pearson correlation coefficients were: anion gap vs glycolate r2 = 0.65 (p = 0.005), bicarbonate vs glycolate r2 = 0.10 (NS) and pH vs glycolate r2 = 0.06 (NS). CONCLUSION: Glycolate has a slow elimination rate and long half-life. Hemodialysis effectively clears glycolate. An increased anion gap correlates with the presence of glycolate. Hemodialysis is projected as useful for ethylene glycol-poisoned patients with anion gap acidosis and low ethylene glycol blood levels.     

Thirteen cystic fibrosis patients, 12 compound heterozygous and one homozygous for the missense mutation G85E: a pancreatic sufficiency/insufficiency mutation with variable clinical presentation

To study the severity of mutation G85E, located in the first membrane spanning domain of the CFTR gene, we studied the clinical features of 13 Spanish patients with cystic fibrosis (CF) carrying this mutation. G85E accounts for about 1% of Spanish CF alleles. One patient was homozygous G85E/G85E and the rest were compound heterozygotes for G85E and other mutations (delta F508 nine patients, delta I507 two patients, and 712-1G > T one patient). The characteristics of the pooled G85E/any mutation group were compared with those of 30 delta F508 homozygotes. Mean age at diagnosis and percentage of ideal height for age were higher in the G85E/any mutation group (4.2 (SD 4.7) v 2.4 (SD 2.3), p < 0.05, and 102.8 (SD 4.7) v 97.8 (SD 4.1), p < 0.01), both probably related to the greater prevalence of pancreatic sufficiency (70% v 0%, p < 0.01). The G85E homozygote was pancreatic sufficient. Sweat sodium levels were slightly higher, and salt loss related problems more frequent, in the G85E/any group. Two of the G85E patients died of respiratory failure aged 6 and 14 years. Striking discordance in the phenotype was observed in two pairs of sibs, one of them dizygotic twins, suggesting that factors, genetic and environmental, other than CFTR genotype are important in determining CF phenotype.     

The fen-phen finale: a study of weight loss and valvular heart disease

Exercise tolerance may be reduced in patients with cystic fibrosis, but it is not always possible to predict this from standard lung function measurements. Formal exercise testing may, therefore, be necessary, and the test should be simple and readily available. We have developed a "3-minute step test" and compared it with the standard 6-minute walking test. Subjects stepped up and down a 15-cm-high single step at a rate of 30 steps per minute for 3 minutes. The effect of the step test on spirometry was tested first in 31 children with CF (mean age, 12.0 years), who had a mean (range) baseline forced expired volume in 1 second (FEV1) of 64% (18-94%) of predicted values. The step test was then compared with the standard 6-minute walk in a further 54 patients with cystic fibrosis (mean age, 12.5 years), with mean (range) baseline FEV1 of 61% (14-103%) of predicted values. Outcome measures were minimum arterial oxygen saturation (SaO2), maximum pulse rate, and the modified Borg dyspnea score. Post-step test spirometry showed mean (95% CI) changes of -1.1% (-6.0 + 3.9%) for forced vital capacity, of -1.6% (-4.2 + 1.1%) for FEV1, and +0.25% (-2.8 + 3.3%) for peak expiratory flow, although 5/31 children showed >15% drop in one or more parameters. The step and walk tests both produced significant changes (P < 0.0001) in all outcomes, with a mean (range) minimum SaO2 of 92% (75-98%) versus 92% (75-97%), a maximum pulse rate of 145 b.p.m. (116-189) versus 132 (100-161), and a Borg score of 2.5 (0-9) versus 1.0 (0-5), respectively. Comparison of the two tests showed that the step test increased breathlessness (mean change Borg score, 2.3 vs. 0.8; P < 0.0001) and pulse rate (mean change, 38% vs. 24%, P < 0.0001) significantly more than the walk, whereas the decrease in SaO2 was similar (mean change, -2.9% vs. -2.6%; P = 0.12). Some patients with a significant drop in SaO2 (>4%) would not have the decrease predicted from their baseline lung function. Reproducibility for the two tests was similar. The step test is quick, simple and portable, and is not dependent on patient motivation. Although the step test is more tiring, its effect on SaO2 is similar to the 6-minute walking test. It is a safe test that may prove to be a valuable measure of exercise tolerance in children with pulmonary disease, although longitudinal studies are now needed.