The cystic fibrosis transmembrane conductance regulator (CFTR) inhibits ENaC through an increase in the intracellular Cl- concentration

Activation of the CFTR Cl- channel inhibits epithelial Na+ channels (ENaC), according to studies on epithelial cells and overexpressing recombinant cells. Here we demonstrate that ENaC is inhibited during stimulation of the cystic fibrosis trans-membrance conductance regulator (CFTR) in Xenopus oocytes, independent of the experimental set-up and the magnitude of the whole-cell current. Inhibition of ENaC is augmented at higher CFTR Cl- currents. Similar to CFTR, ClC-0 Cl- currents also inhibit ENaC, as well as high extracellular Na+ and Cl- in partially permeabilized oocytes. Thus, inhibition of ENaC is not specific to CFTR and seems to be mediated by Cl-.

Rehabilitation outcomes following percutaneous coronary interventions (PCI)

This prospective study evaluated the effect of an individualized, comprehensive, home-based cardiac rehabilitation program combining exercise training with risk factor modification and psychosocial counseling on risk factors, psychological wellbeing, functional capacity, and work resumption in 99 post-percutaneous coronary interventions (PCI) patients randomized to control (standard care plus telephone follow-up, n = 49) or intervention (individualized, comprehensive, home-based cardiac rehabilitation, n = 50) groups. Data were collected at time 1 (T-1) during hospital admission, time 2 (T-2) approximately 2 months post-PCI, and time 3 (T-3) approximately 12 months post-PCI. Results suggest that the allocation to an individualized, comprehensive, home-based cardiac rehabilitation program provided more advantageous outcomes. At both follow-ups, the intervention group showed within-group improvement in serum cholesterol levels (P < 0.02; P < 0.01) and exercise participation (P < 0.001; P < 0.001) with differences in exercise participation favoring the intervention group (P < 0.01) at T-2 Repeated measures ANOVA showed significant improvements over time in body mass index (BMI) (P < 0.01), psychological well-being (P < 0.001), and functional capacity (P < 0.001) for both groups. More patients in the intervention group had returned to work at T-2 (P < 0.001) and did so more quickly (P < 0.01). These findings suggest that an individualized, comprehensive, home-based cardiac rehabilitation program improves risk factor profiles and work resumption patterns for patients following PCI. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Energy expenditure and the body cell mass in cystic fibrosis

Poor nutritional status in patients with cystic fibrosis (CF) is associated with severe lung disease, and possible causative factors include inadequate intake, malabsorption, and increased energy requirements. Body cell mass (which can be quantified by measurement of total body potassium) provides an ideal standard for measurements of energy expenditure. The aim of this study was to compare resting energy expenditure (REE) in patients with CF with both predicted values and age-matched healthy children and to determine whether REE was related to either nutritional status or pulmonary function. REE was measured by indirect calorimetry and body cell mass by scanning with total body potassium in 30 patients with CF(12 male, mean age = 13.07 +/- 0.55 y) and 18 healthy children (six male, mean age = 12.56 +/- 1.25 y). Nutritional status was expressed as a percentage of predicted total body potassium; Lung function was measured in the CF group by spirometry and expressed as the percentage of predicted forced expiratory volume in 1 s. Mean REE was significantly increased in the patients with CF compared with healthy children (119.3 +/- 3.1% predicted versus 103.6 +/- 5% predicted, P < 0.001) and, using multiple regression techniques, REE for total body potassium was significantly increased in patients with CF (P = 0.0001). There was no relation between REE and nutritional status or pulmonary disease status in the CF group. In conclusion, REE is increased in children and adolescents with CF but is not directly related to nutritional status or pulmonary disease. Nutrition 2001;17:22-25. (C)Elsevier Science Inc. 2001.

Forced emigration, favourable outcomes

The discipline of public health and preventive medicine in Australia and New Zealand had its genesis in the advocacy of 18th and 19th century military pioneers. Military (Royal Navy and British Army) surgeons were posted to Australia as part of their non-discretionary duty. Civilian doctors emigrated variously for adventure, escapism and gold fever. One group, a particularly influential group disproportionate to their numbers, came in one sense as forced emigrants because of chronic respiratory disease in general, and tuberculosis in particular. Tuberculosis was an occupational hazard of 19th century medical and surgical practice throughout western Europe. This paper analyses six examples of such emigration which had, perhaps unforeseen at the time, significant results in the advancement of public health. Such emigration was in one sense voluntary, but in another was forced upon the victims in their quest for personal survival. In Australia, such medical individuals became leading advocates and successful catalysts for change in such diverse fields as social welfare, public health, the preventive aspects of medical practice, child health, nutrition and medical education. A number of such public health pioneers today have no physical memorials; but their influence is to be seen in the ethos of medical practice in Australia and New Zealand today. Their memory is further perpetuated in the names of Australian native wildflowers and trees that symbolise not only a healthy environment but the longterm investment, accrued with interest, of the institution of public health measures for which their advocacy achieved much success.

Outcomes of cephalosporin treatment for serious infection due to apparently susceptible organisms producing extended-spectrum b-Lactamases: Implications for the clinical microbiology laboratory

Although extended-spectrum beta-lactamases (ESBLs) hydrolyze cephalosporin antibiotics, some ESBL-producing organisms are not resistant to all cephalosporins when tested in vitro. Some authors have suggested that screening klebsiellae or Escherichia coli for ESBL production is not clinically necessary, and when most recently surveyed the majority of American clinical microbiology laboratories did not make efforts to detect ESBLs, We performed a prospective, multinational study of Klebsiella pneumoniae bacteremia and identified 10 patients who were treated for ESBL-producing K. pneumoniae bacteremia with cephalosporins and whose infecting organisms were not resistant in vitro to the utilized cephalosporin. In addition, we reviewed 26 similar cases of severe infections which had previously been reported. Of these 36 patients, 4 had to be excluded from analysis. Of the remaining 32 patients, 100% (4 of 4) patients experienced clinical failure when MICs of the cephalosporin used for treatment were in the intermediate range and 54% (15 of 28) experienced failure when MICs of the cephalosporin used for treatment were in the susceptible range, Thus, it is clinically important to detect ESBL production by klebsiellae or E, coli even when cephalosporin MICs are in the susceptible range (less than or equal to 8 mug/ml) and to report ESBL-producing organisms as resistant to aztreonam and all cephalosporins (with the exception of cephamycins).

Long-term outcomes of genetic counseling in women at increased risk of developing hereditary breast cancer Information,

This multicenter study evaluated the impact of genetic counseling in 218 women at risk of developing hereditary breast cancer. Women were assessed prior to counseling and 12-month post-counseling using self-administered, mailed questionnaires. Compared to baseline, breast cancer genetics knowledge was increased significantly at follow-up. and greater increases in knowledge were associated with educational level. Breast cancer anxiety decreased significantly from baseline to follow-up, and these decreases were associated with improvements in perceived risk. A significant decrease in clinical breast examination was observed at the 12-month follow-up. Findings suggest that women with a family history of breast cancer benefit from attending familial cancer clinics as it leads to increases in breast cancer genetics knowledge and decreases in breast cancer anxiety. The lowered rates of clinical breast examination indicate that the content of genetic counseling may need to be reviewed to ensure that women receive and take away the right message. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Outcomes of transient evoked otoacoustic emission testing in 6-year-old school children: A comparison with pure tone screening and tympanometry

Objectives: (1) To establish test performance measures for Transient Evoked Otoacoustic Emission testing of 6-year-old children in a school setting; (2) To investigate whether Transient Evoked Otoacoustic Emission testing provides a more accurate and effective alternative to a pure tone screening plus tympanometry protocol. Methods: Pure tone screening, tympanometry and transient evoked otoacoustic emission data were collected from 940 subjects (1880 ears), with a mean age of 6.2 years. Subjects were tested in non-sound-treated rooms within 22 schools. Receiver operating characteristics curves along with specificity, sensitivity, accuracy and efficiency values were determined for a variety of transient evoked otoacoustic emission/pure tone screening/tympanometry comparisons. Results: The Transient Evoked Otoacoustic Emission failure rate for the group was 20.3%. The failure rate for pure tone screening was found to be 8.9%, whilst 18.6% of subjects failed a protocol consisting of combined pure tone screening and tympanometry results. In essence, findings from the comparison of overall Transient Evoked Otoacoustic Emission pass/fail with overall pure tone screening pass/fail suggested that use of a modified Rhode Island Hearing Assessment Project criterion would result in a very high probability that a child with a pass result has normal hearing (true negative). However, the hit rate was only moderate. Selection of a signal-to-noise ratio (SNR) criterion set at greater than or equal to 1 dB appeared to provide the best test performance measures for the range of SNR values investigated. Test performance measures generally declined when tympanometry results were included, with the exception of lower false alarm rates and higher positive predictive values. The exclusion of low frequency data from the Transient Evoked Otoacoustic Emission SNR versus pure tone screening analysis resulted in improved performance measures. Conclusions: The present study poses several implications for the clinical implementation of Transient Evoked Otoacoustic Emission screening for entry level school children. Transient Evoked Otoacoustic Emission pass/fail criteria will require revision. The findings of the current investigation offer support to the possible replacement of pure tone screening with Transient Evoked Otoacoustic Emission testing for 6-year-old children. However, they do not suggest the replacement of the pure tone screening plus tympanometry battery. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Rehabilitation outcomes for brain injured patients in Australia: functional status, length of stay and discharge destination

This study describes the rehabilitation length of stay (LOS), discharge destination and discharge functional status of 149 patients admitted with traumatic brain injury (TBI) to an Australian hospital over a 5-year period. Hospital charts of patients admitted between 1993-1998 were reviewed. Average LOS over the 5-year time period was 61.8 days and only decreased nominally over this time. Longer LOS was predicted by lower admission motor FIM scores and presence of comorbidities. Mean admission and discharge motor FIM scores were 58 and 79, which represented a gain of 21 points. Higher discharge motor FIM scores were predicted by higher admission motor FIM scores and younger age. FIM gain was predicted by cognitive status and age. Most patients, 88%, were discharged back to the community, with 30% changing their living setting or situation. Changing living status was predicted by living alone and having poorer functional status on admission.

Surgical outcomes of a randomized prospective trial involving patients with a proximal femoral fracture

Background: An orthopaedic management/patient-focused care unit (OMPFCU) involving a dedicated orthopaedic-geriatrics liaison team was established at the Royal Brisbane Hospital in 1994 in an effort to safely accelerate rehabilitation of patients with proximal femoral fractures. Methods: The surgical outcomes of the patients were monitored in order to determine whether accelerated rehabilitation had any significant adverse effects on the surgical outcomes, measured by mortality, readmission to hospital, deep wound infection, fracture union delay, mobility and the revision surgery rate. Results: No significant difference was recorded in mortality and morbidity, deep wound infection and revision surgery rates between patients in the Royal Brisbane Hospital OMPFCU and those in standard care in the orthopaedic surgery wards. Conclusion: Accelerated rehabilitation for patients with a proximal femoral fracture in a major teaching hospital can be accomplished safely.

Single institution outcomes of treatment of severe aplastic anaemia

Background: In severe aplastic anaemia, the treatment of choice for young patients with a human leucocyte antigen-matched sibling is now established as allogeneic bone marrow transplantation (BMT). In older patients and in those without a matched sibling donor, immunosuppressive therapy is the usual first option. 'Alternative' marrow donors are emerging as an option for those without a matched sibling donor. Aims: To review 10 years of local experience in treating severe aplastic anaemia with BMT and immunosuppressive therapy with emphasis on long-term outcomes. Methods: A retrospective analysis was performed of all patients with severe aplastic anaemia presenting to the Royal Brisbane and Royal Children's Hos- pitals between 1989 and 1999. Data were abstracted regarding patient demographics, pretreatment characteristics and outcome measures, including response rates, overall survival and long-term complications. Results: Twenty-seven consecutive patients were identified, 12 treated with immunosuppression alone and 15 with BMT. In these two groups, transfusion independence was attained in 25% and 100%, respectively, with overall survival being 36% and 100%, respectively. Those treated with immunosuppression were significantly older (median 41.5 versus 22 years, P = 0.008). Long-term survivors of either treatment had extremely low morbidity. Three patients carried pregnancies to term post-transplant. Three patients received alternative donor BMT with correspondingly excellent survival. Conclusions: Patients treated with allogeneic BMT for severe aplastic anaemia enjoyed extremely good long-term survival and minimal morbidity. Patients treated with immunosuppressive therapy had a poorer outcome reflecting their older age and different usage of therapies over the past decade. Optimal treatment strategies for severe aplastic anaemia remain to be determined.

Child-Pugh class, nutritional indicators and early liver transplant outcomes

Background/Aims: Patients with chronic liver disease undergoing liver transplantation have reduced body fat and muscle mass. The extent to which nutritional indicators and Child-Pugh class are predictive of postoperative outcome in adults is unclear. The aims of this study were to determine in adult patients undergoing transplant 1) the influence of preoperative Child-Pugh class and nutritional indicators on early transplant outcomes and one-year survival, 2) the relationship between nutritional indicators and Child-Pugh class and disease type. This study included 80 patients (1990-1994). Methodology: The nutritional indicators utilized were grip strength, triceps skinfold thickness and uncorrected mid-arm muscle area. Measured outcomes were ventilator time, intensive care stay, postoperative hospital stay and one-year survival. Results: Early morbidity was determined in survivors. Child-Pugh class C patients required longer ventilation and spent more time in the intensive care unit than Child-Pugh classes A and B. No significant relationships were found length of hospital stay. Relationships between the nutritional indicators (when controlled for Child-Pugh class) and early morbidity could not be determined due;to insufficient data. No relationship was established between one-year survival and Child-Pugh class or the nutritional indicators. Grip strength and mid-arm muscle area were lower in the patients in Child-Pugh:classes B and C. Parenchymal liver disease was associated with lower grip strength and mid-arm muscle area when compared to cholestatic disease. Conclusions: Child-Pugh class C is associated with greater early postoperative morbidity. Advanced Child-Pugh class is also associated with diminished muscle status and parenchymal disease.

Energy cost of physical activity in cystic fibrosis

Objective: The purpose of this study was to compare the energy cost of standardized physical activity (ECA) between patients with cystic fibrosis (CF) and healthy control subjects. Design: Cross-sectional study using patients with CF and volunteers from the community. Setting: University laboratory. Subjects: Fifteen patients (age 24.6 +/- 4.6 y) recruited with consent from their treating physician and 16 healthy control subjects (age 25.3 +/- 3.2) recruited via local advertisement. Interventions. Patients and controls walked on a computerised treadmill at 1.5 km/h for 60 min followed by a 60 min recovery period and, on a second occasion, cycled at 0.5 kp (kilopond), 30 rpm followed by a 60 min recovery. The ECA was measured via indirect calorimetry. Resting energy expenditure (REE), nutritional status, pulmonary function and genotype were determined. Results: The REE in patients was significantly greater than the REE measured in controls (P = 0.03) and was not related to the severity of lung disease or genotype. There was a significant difference between groups when comparing the ECA for walking kg root FFM (P = 0.001) and cycling kg root FFM (P = 0.04). The ECA for each activity was adjusted (ECA(adj)) for the contribution of REE (ECA kJ kg root FFM 120 min(-1) - REE kJ kg root FFM 120 min(-1)). ECA(adj) revealed a significant difference between groups for the walking protocol (P = 0.001) but no difference for the cycling protocol (P = 0.45). This finding may be related to the fact that the work rate during walking was more highly regulated than during cycling. Conclusions ECA in CF is increased and is likely to be explained by an additional energy-requiring component related to the exercise itself and not an increased REE. Sponsorship. The Prince Charles Hospital Foundation; MLR was in receipt of a QUTPRA Scholarship.