Using the Lower Limit of Normal Instead of the Conventional Cutoff Values to Define Predictors of Pulmonary Function Impairment in Subjects With Chronic Heart Failure.

BACKGROUND: Using the newer lower limit of normal criterion instead of the conventional cutoff values to define pulmonary function abnormalities may result in different predictors of pulmonary function impairment in patients with heart failure. Therefore, we assessed predictors of pulmonary function impairment in subjects with chronic heart failure according to the lower limit of normal in comparison with conventional cutoff values. METHODS: In this prospective cross-sectional study, 164 chronic heart failure subjects (age 68 ± 10 y, 78% men, 88% New York Heart Association class I-II) with left ventricular ejection fraction <40% underwent pulmonary function tests. Predictors of pulmonary function impairment were assessed using the lower limit of normal and conventional cutoff values (ie, 80% predicted value and the fixed ratio of FEV1/FVC <0.7). RESULTS: The lower limit of normal criterion identified an extra independent predictor of diffusion impairment compared with the 80% predicted value; in addition to body mass index, pack-years, and alveolar volume, female sex also turned out to be an independent predictor. A smoking history of ≥10 pack-years was a significant predictor of diffusion impairment and airway obstruction using the lower limit of normal criterion but not using the conventional cutoff values. However, lowering the cutoff points of conventional criteria to match the more stringent lower limit of normal and thus avoid overdiagnosis of diffusion impairment and airway obstruction in the elderly produced similar results as the lower limit of normal. CONCLUSIONS: The lower limit of normal identifies more predictors of diffusion impairment and airway obstruction compared with conventional cutoff values in subjects with chronic heart failure with left ventricular systolic dysfunction. However, lowering the conventional cutoff points yielded similar results as the lower limit of normal. (ClinicalTrials.gov registration NCT01429376.).

Bronchodilator responsiveness in patients with chronic heart failure.

OBJECTIVE: The aim of this study was to evaluate the effect of inhaled bronchodilators on pulmonary function and dyspnea in patients with chronic heart failure (HF). BACKGROUND: Conflicting data exist on whether bronchodilators may improve pulmonary function and dyspnea in patients with chronic HF. METHODS: In this retrospective observational study we analyzed data of 116 chronic HF outpatients with systolic dysfunction who underwent spirometry and Borg dyspnea measurements before and after inhalation of 400 µg salbutamol and 80 µg ipratropium. Patients with chronic obstructive pulmonary disease (COPD) or asthma were excluded. RESULTS: Bronchodilators fully reversed airway obstruction (AO) in 25 of 64 (39.1%) patients with pre-bronchodilator AO. All spirometric measurements, except for forced vital and inspiratory capacities, improved significantly post-bronchodilation. Absolute and percent improvements in forced expiratory volume in 1 s (FEV1) were more pronounced in patients with persistent AO post-bronchodilation compared to those without AO (0.19 ± 0.18 L and 8.4 ± 7.3% versus 0.11 ± 0.12 L and 4.3 ± 4.0%, p < 0.05). Significant bronchodilator responsiveness of FEV1 (>200 mL and >12%) was noted in 12.1% and was more frequent in patients with persistent AO and fully reversible AO than in those without AO (23.1% and 16.0% versus 1.9%, p < 0.05). We measured a small, albeit significant improvement in dyspnea (0.7 ± 1.2 versus 0.9 ± 1.3, p = 0.002). CONCLUSIONS: Inhaled bronchodilators may have an additional role in the management of patients with chronic HF because of their potential to improve pulmonary function, especially in those with AO. The clinical usefulness and possible adverse events of bronchodilators need to be further established.

Allogeneic hematopoietic stem cell transplantation and norovirus gastroenteritis: a previously unrecognized cause of morbidity.

BACKGROUND: A retrospective study of the clinical, epidemiologic, and virologic features of norovirus gastroenteritis in 12 adult allogeneic hematopoietic stem cell transplant (HSCT) recipients. METHODS: Norovirus infection was diagnosed by reverse-transcriptase polymerase chain reaction. Strains were genotyped by nucleic acid sequence of the most highly conserved region of the norovirus gene encoding the capsid S (shell) domain. RESULTS: Ten of 12 patients presented with vomiting of short duration, but diarrhea was present in all. The median time from onset to norovirus diagnosis was 1 month (range, 0.25-6.0 months). Eleven patients were receiving immunosuppression when norovirus infection was diagnosed: 8 for graft-versus-host disease (GVHD) in an organ other than gut, 1 for previous gut GVHD, and 2 for presumed gut GVHD that proved to be norovirus gastroenteritis. Six patients required enteral or parenteral nutrition for severe weight loss. In 10 patients, diarrhea lasted a median of 3 months (range, 0.5-14 months) and virus was shed at a high level throughout. The remaining 2 patients died after 4 months of diarrhea (one died of unrelated complications, and the other died of malnutrition). The noroviruses found were GII (untyped), GII-3, GII-4, and GII-7 in 1, 1, 9, and 1 patients, respectively. Eleven of the 12 patients had acquired their infection in the community. Phylogenetic analysis of the GII-4 strains demonstrated that all differed. CONCLUSIONS: Noroviruses are a hitherto unsuspected cause of prolonged morbidity and mortality in adults after allogeneic HSCT. The use of reverse-transcriptase polymerase chain reaction to detect high viral load levels in feces distinguishes norovirus gastroenteritis from gut GVHD.

Fractional efflux and net change in cellular cholesterol content mediated by sera from mice expressing both human apolipoprotein AI and human lecithin:cholesterol acyltransferase genes.

Human lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the metabolism of cholesterol and is postulated to participate in the physiological process called reverse cholesterol transport. We have used transgenic mice (Tgm) expressing either both human apolipoprotein AI (apo AI) and human LCAT genes or only the human apo AI gene (HuAILCAT or HuAI Tgm, respectively) to assess the consequences of LCAT overexpression on serum lipid and lipoprotein profiles and on the ability of each serum to promote bidirectional flux of cholesterol between serum and Fu5AH hepatoma cells. Mean serum LCAT activity of HuAILCAT Tgm was 2-fold increased compared to the HuAI group (48+/-9 vs. 24+/-5 nmol/ml per h, P<0.01 for HuAILCAT and HuAI Tgm, respectively) and the cholesterol esterification rates were not significantly different between the two groups of animals (66+/-11 vs. 74+/-18 nmol/ml per h for HuAILCAT and HuAI Tgm, respectively). HuAILCAT Tgm exhibited higher total cholesterol serum values (2.3-fold) due to an increase in both HDL-cholesterol (1. 9-fold) and non-HDL-cholesterol (3-fold). The HDL particles from HuAILCAT Tgm were relatively phospholipid depleted and cholesterol enriched compared to HuAI mice. When cells were incubated for six hours with the mouse serum, the fractional efflux of radiolabeled cholesterol was slightly increased with the HuAILCAT Tgm (1.2-fold) but the increase in intracellular cholesterol content was also 2-fold higher than with the HuAI Tgm. Fu5AH can be viewed as a model for the evaluation of bidirectional flux of cholesterol in SR-BI-rich cells. In this model LCAT overexpression in mice, by increasing both HDL and non-HDL-cholesterol, mostly enhances the uptake of cholesterol by the cells, which would be of benefit for the last step of reverse cholesterol transport in hepatocytes.

The influence of medial and lateral placement of orthotic wedges on loading of the plantar aponeurosis.

BACKGROUND: Repetitive trauma and overuse of the plantar aponeurosis are believed to be causal factors of plantar fasciitis. Therefore, it is important to know how an orthosis influences loading of the plantar aponeurosis. The aim of this study was to quantify strain in the plantar aponeurosis in cadaveric feet with the use of various combinations of orthotic wedges. METHODS: An in vitro test that simulated static stance was used to determine the loading characteristics of the plantar aponeurosis. A differential variable reluctance transducer was operatively implanted into the plantar aponeurosis of nine fresh-frozen cadaveric lower limbs. Each specimen was mounted in an electromechanical testing machine that applied an axial load of as much as 900 newtons to the tibia. Eight different combinations of test conditions, in which wedges (each with a 6-degree incline) were or were not positioned under the medial and lateral aspects of the forefoot and hindfoot, were evaluated, with the plantigrade foot used as a neutral control. RESULTS: Each of the test conditions that involved a wedge under the forefoot resulted in strain that was significantly different from that in the neutral control. A wedge under the lateral aspect of the forefoot decreased strain in the plantar aponeurosis, and a wedge under the medial aspect increased strain (p < 0.05). The test conditions that involved a wedge under the hindfoot but not under the forefoot resulted in strains that were not significantly different from those in the neutral control (p > 0.05). CONCLUSIONS: A wedge under the lateral aspect of the forefoot transmits loads through the lateral support structures of the foot, locking the calcaneocuboid joint and decreasing strain in the plantar aponeurosis. A wedge under the medial aspect of the forefoot transmits loads through the medial support structures of the foot, which produces a truss-like action that increases strain in the plantar aponeurosis.

Treatment of portwine stains using the pulsed dye laser.

Five years of clinical experience of the treatment of portwine stains using the flashlamp-pumped dye laser is presented. The dye laser, when turned to a wavelength of 577 nanometres with a short pulsewidth of the order of 340 microseconds, may be used to target selectively the dilated vasculature constituting the lesion. Patients with ages ranging from 5-45 years were treated under general anaesthetic using a computer controlled scanning system developed by the authors. Several repeat treatments were found to be necessary. Results are presented ranging from total eradication of the lesion to marginal lightening only. No scarring of the treated sites was evident.

Q-switched ruby laser treatment of tattoos; a 9-year experience.

Nine years of clinical experience of the application of the Q-switched ruby laser to the removal of tattoos is presented. This laser achieves optimal removal of blue/black amateur tattoos by its selective interaction with the dermal suspensions of pigment which constitute the tattoos. The scar free cosmesis thus achieved is a considerable improvement on non-specific laser techniques whereby the laser is absorbed to a comparable degree in both pigmented and non-pigmented tissue. Long-term results are analysed and it is noted that a variety of professional tattoos may also respond to treatment. The mechanisms and appearance are discussed and correlated with short-term healing processes. It is found that power densities in the range 1200-2800 GW/m2 are most suitable. Appropriate dosimetry can be witnessed by the appearance of opaque intradermal vacuoles corresponding to the vaporization of the tissue water surrounding the pigment suspensions. Treatment by Q-switched ruby laser offers a viable scar-free option for a wide range of dark tattoos, leading to a more acceptable clinical outcome in most cases than other current therapies.

Biomechanical assessment of patients treated by joint surgery.

Surgical replacement of lower limb joints has been practised for twenty years although there is little quantitative information on loads transmitted either by implants or by other related joints. The results of tests are presented which evaluate the variation in external forces developed between the ground and foot during walking, together with the configuration of the lower limbs and the moments acting about the hips and knees. Two groups of patients were investigated; patients who were assessed prior to joint replacement and at intervals thereafter, and patients for whom the Girdlestone procedure was performed following a failed implant. The results area compared with those from similar tests on clinically normal subjects. There is a significant improvement post-operatively in the mechanical aspects of hip function for the replacement patients. The improvement continues after the first six months post-operatively and may result in abnormally high loading at other joints. At twelve months the performance of the patients with joint replacement differs significantly from the normal subjects and is generally better than the Girdlestone patients.