24800503
Clinical significance of Aspergillus sensitisation in bronchial asthma.
Numerous studies have suggested a link between fungal sensitisation and severity of asthma. However, few studies have specifically evaluated the relationship between Aspergillus sensitisation and asthma severity. This study was aimed at investigating the clinical significance of Aspergillus sensitisation in asthma. In this prospective cross-sectional study, patients with asthma were subjected to pulmonary function test and an intradermal Aspergillus skin test (AST) apart from a detailed clinical history and physical examination. Assessment of asthma severity was carried according to the Global Initiative for Asthma (GINA) recommendations, Asthma Control Test (ACT) and the mini Asthma Quality of Life Questionnaire (mini AQLQ). Based on AST, the cases were dichotomised into Aspergillus-sensitive and AST-negative groups. There were 417 (193 males, 224 females; mean age, 34 years) asthmatic patients of whom 219 (52.5%) showed Aspergillus sensitisation. The severity of disease as per the GINA criteria and the dose of ICS required for asthma control were similar in the two groups. The Aspergillus-sensitive group had poorer pulmonary function than the AST-negative group [AST positive vs. negative: percentage predicted mean (SD) forced expiratory volume in the first second: 73.1(23.8) vs. 77.9(22.7), P = 0.04; mean (SD) FEV(1) /forced vital capacity (FVC) ratio: 68.2(13.3) vs. 74.3(15.7), P = 0.0001]. The mini AQLQ scores were similar in the two groups. In the ACT, the numbers of patients in the domain pertaining to nocturnal awakenings were significantly higher in the Aspergillus-sensitive group (P = 0.014). There was a weak association between Aspergillus sensitisation and severity of asthma. Whether Aspergillus sensitisation is causally linked to asthma severity remains to be seen.
22528299
Pulmonary hypertension as a presenting manifestation of allergic bronchopulmonary aspergillosis.
The case of a 46-year-old lady who presented with respiratory failure and pulmonary hypertension in the absence of clinical signs of asthma or bronchiectasis, and in whom a diagnosis of allergic bronchopulmonary aspergilloma [ABPA] was made subsequently on the basis of radiological and laboratory investigations is reported. Symptomatic and objective improvement was seen with corticosteroid therapy. To the best of the authors' knowledge, such an occurrence has not been reported previously. This case highlights the importance of keeping a high index of suspicion while investigating a patient with pulmonary hypertension in whom the aetiology is not apparent on initial evaluation. Identification of the disease, in its early-stage, can prevent progression to bronchiectasis and fibrotic lung disease, and thus, patients can be saved from the morbidity related to end-stage disease.
33491888
Noninvasive ventilation in ARDS caused by Mycobacterium tuberculosis: report of three cases and review of literature
45999589
Noninvasive ventilation in acute heart failure.
26068481
Efficacy and safety of iodopovidone pleurodesis through tube thoracostomy.
OBJECTIVE
To evaluate the efficacy and safety of iodopovidone as an agent for pleurodesis through tube thoracostomy in patients with recurrent pleural effusions and pneumothorax.


METHODS
This was a prospective study in which pleurodesis was performed with a solution of 20 mL 10% iodopovidone and 80 mL normal saline solution infused through a tube thoracostomy and left in the pleural cavity for 4 h.


RESULTS
A total of 64 patients (34 men) with a mean (+/-SD) age of 47.1 +/- 15.4 years were included. There were 37 cases of pleural effusion and 27 of pneumothorax. A complete response (neither reaccumulation of fluid nor recurrence of pneumothorax) was obtained in 32 (86.5%) patients with pleural effusion and 25 (92.6%) patients with pneumothorax. A second procedure (i.e. repeated pleurodesis) was attempted successfully in four patients in the pleural effusion group. All patients experienced chest pain to a varying degree as recorded on a Visual Analogue Scale (median 50.5, range 10-95). Seven patients developed fever and one immunocompromised patient developed empyema following the procedure. There were no recurrences at a median follow up of 5 months (range 3-15 months) in the pleural effusion group, and 13 months (range 6-24 months) in the pneumothorax group.


CONCLUSIONS
Iodopovidone can be used as an effective and safe agent for (chemical) pleurodesis (through tube thoracostomy), which is inexpensive and readily available.
3038618
Is the mortality higher in the pulmonary vs the extrapulmonary ARDS? A meta analysis.
BACKGROUND AND AIM
ARDS can occur from the following two pathogenetic pathways: a direct pulmonary injury (ARDSp); and an indirect injury (ARDSexp). The predisposing clinical factor can influence the pathogenesis and clinical outcome of ARDS. This metaanalysis was aimed at evaluating whether there is any difference in mortality between the two groups.


METHODS
We searched the MEDLINE, EMBASE, and CINAHL databases for relevant studies published from 1987 to 2007, and included studies that have reported mortality in the two groups of ARDS. We calculated the odds ratio (OR) and 95% confidence interval (CI) to assess mortality in patients with ARDSp vs patients with ARDSexp and pooled the results using three different statistical models.


RESULTS
Our search yielded 34 studies. In all, the studies involved 4,311 patients with 2,330 patients in the ARDSp group and 1,981 patients in the ARDSexp group. The OR of mortality in ARDSp group compared to the ARDSexp group was 1.11 (95% CI, 0.88 to 1.39), as determined by the random-effects model; 1.04 (95% CI, 0.92 to 1.18), as determined by the fixed-effects model; and 1.04 (95% CI, 0.92 to 1.18), as determined by the exact method, indicating that mortality is similar in the two groups. The mortality was no different whether the studies were classified as prospective (OR, 1.15; 95% CI, 0.87 to 1.51) or retrospective (OR, 1.01; 95% CI, 0.61 to 1.69); small (OR, 1.11; 95% CI, 0.77 to 1.60) or large (OR, 1.1; 95% CI, 0.82 to 1.49); or observational (OR, 1.10; 95% CI, 0.82 to 1.49) or interventional (OR, 0.97; 95% CI, 0.79 to 1.19). There was methodological and statistical heterogeneity (I(2), 50.9%; 95% CI, 21.3 to 66.2%; chi(2) statistic, 67.22; p = 0.0004).


CONCLUSIONS
The results of this study suggest that there is no difference in mortality between these two groups. Further studies should focus on specific etiologies within the subgroups rather than focusing on the broader division of ARDSp and ARDSexp.
33593233
Home blood pressure monitoring improves the diagnosis of hypertension in hemodialysis patients.
Using interdialytic ambulatory blood pressure (BP) recordings as the reference standard, we compared the performance of routine, standardized and home BP monitoring in 104 predominantly black patients on chronic hemodialysis for at least 3 months. Dialysis unit BP recordings were averaged over 2 weeks and home BP over 1 week. Awake ambulatory BP of > or =135 mmHg systolic or > or =85 mmHg diastolic was taken as evidence of hypertension. Average awake ambulatory BP was 128.1+/-21.6/73.5+/-13.5 mmHg, home BP 141.3+/-21.9/78.7+/-11.9 mmHg, standardized pre-dialysis BP 141.7+/-22.6/74.2+/-13.5 mmHg and post-dialysis 119.9+/-20.5/69.1+/-13.1 mmHg, routine pre-dialysis 145.4+/-21.8/79.0+/-13.1 mmHg and post-dialysis 131.5+/-19.2/72.5+/-11.4 mmHg. Sixty-three percent of the patients had well-controlled BP by ambulatory BP monitoring and isolated diastolic hypertension was rare (3%). The standard deviation of the differences between ambulatory and routine pre-dialysis BP was 17.6 mmHg, routine post-dialysis was 16.1 mmHg, standardized pre-dialysis was 16.4 mmHg, standardized post-dialysis was 14.1 mmHg, and home BP was 14.2 mmHg. The area under receiver operating characteristic curves was similar for home and standardized BP but lower for routine BP. Home systolic BP of > or =150 mmHg averaged over 1 week had the best combination of sensitivity (80%) and specificity (84.1%) in diagnosing systolic hypertension--present in 94% of the hypertensive dialysis patients. Home BP monitoring is similar to standardized recording of BP in hemodialysis patients. A systolic BP threshold of 150 mmHg at home averaged over 1 week serves as a useful predictor of hypertension diagnosed by ambulatory BP monitoring.
10671348
Structural analysis of botulinum neurotoxin serotype F light chain: implications on substrate binding and inhibitor design.
The seven serologically distinct Clostridium botulinum neurotoxins (BoNTs A-G) are zinc endopeptidases which block the neurotransmitter release by cleaving one of the three proteins of the soluble N-ethylmaleimide-sensitive-factor attachment protein receptor complex (SNARE complex) essential for the fusion of vesicles containing neurotransmitters with target membranes. These metallopeptidases exhibit unique specificity for the substrates and peptide bonds they cleave. Development of countermeasures and therapeutics for BoNTs is a priority because of their extreme toxicity and potential misuse as biowarfare agents. Though they share sequence homology and structural similarity, the structural information on each one of them is required to understand the mechanism of action of all of them because of their specificity. Unraveling the mechanism will help in the ultimate goal of developing inhibitors as antibotulinum drugs for the toxins. Here, we report the high-resolution structure of active BoNT/F catalytic domain in two crystal forms. The structure was exploited for modeling the substrate binding and identifying the S1' subsite and the putative exosites which are different from BoNT/A or BoNT/B. The orientation of docking of the substrate at the active site is consistent with the experimental BoNT/A-LC:SNAP-25 peptide model and our proposed model for BoNT/E-LC:SNAP-25.
1031032
Developing a self-administered CKD symptom assessment instrument.
BACKGROUND
Current disease-centred therapies for CKD focus on preserving the GFR but often ignore patient-reported symptoms. This purpose of this report is to describe the development of an instrument to measure the presence and severity of a wide range of symptoms commonly attributable to CKD.


METHODS
A 37-item questionnaire was administered along with the Kidney Disease Quality of Life instrument to 92 patients with CKD not on dialysis (24% black, 5% women, mean age 68 years, 68% with diabetes mellitus). To discover groups of symptoms, agglomerative cluster analysis followed by exploratory common factor analysis was performed. Construct validity, internal reliability, convergent and discriminant validity, test-retest reliability and finally the association of various symptom domains with objective measurements such as estimated GFR and haemoglobin were tested.


RESULTS
The top five symptoms of at least moderate severity in decreasing order of prevalence were 'tire easily', limited physical activity, nocturia, joint pain and 'stop and rest often'. Four common factors emerged that could be broadly classified into neuropsychiatric, cardiovascular, uraemia and anaemia symptoms accounting for 73% of the total variance in the sample. The coefficient alpha for each of these factors approached 0.9. The test-retest reliability in 41 patients over 8 weeks was likewise high. There was good convergent and divergent validity. However, there was little relationship between estimated GFR and symptom scores.


CONCLUSIONS
The assessment of symptom burden among patients with CKD may be facilitated by incorporating this instrument in routine practice and clinical trials.
21916120
Treated hypertension and the white coat phenomenon: Office readings are inadequate measures of efficacy.
To better define the prevalence of white coat hypertension (WCH) among patients with type 2 diabetes mellitus and to estimate the magnitude of white coat effect (WCE), before and after antihypertensive therapy, we gathered data from an open-label forced-titration study of a combination of antihypertensive drugs that was titrated sequentially, in the order amlodipine, olmesartan, and hydrochlorothiazide, over an 18-week period among 187 patients with type 2 diabetes mellitus. WCH was defined as daytime ambulatory blood pressure (BP) of 135/85 mm Hg or less, but clinic BP of 140/90 mm Hg or more. WCE was obtained as the mean difference between clinic and daytime ambulatory BP. At baseline, the prevalence of WCH was 12%; all but one subject had WCE of >10/5 mm Hg. After treatment, the prevalence of WCH had increased to 39% (P < .001). In the overall population, at baseline, the mean (±SD) WCE for systolic BP was 10.4 ± 10.9 mm Hg and 3.7 ± 8.6 mm Hg for diastolic BP. After treatment, the reduction in systolic WCE was 3.01 ± 0.93 (SE; P < .0001); no reduction was seen for diastolic WCE. Among patients treated with amlodipine-olmesartan combination, WCE at baseline was 11 mm Hg systolic and was attenuated to -0.9 mm Hg. Among patients treated with amlodipine-olmesartan-hydrochlorothiazide combination, systolic WCE was similar at baseline (10.1 mm Hg) and at end of therapy (8.1 mm Hg). Mean systolic difference between dual and triple therapy of 9.9 mm Hg, SE 2.98 was significant (P < .001). The drop in diastolic WCE from 6.4 with dual therapy to -1.2 with triple therapy was also significant (mean difference 7.6, SE 2.2; P < .001). In conclusion, the prevalence of WCH increases three-fold with treatment as a result of fewer patients having sustained hypertension. Thus, out-of-office BP monitoring especially among treated hypertensive patients with type 2 diabetes is necessary to provide better assessment of overall BP and response to treatment.
6650721
GFR, proteinuria and circadian blood pressure.
BACKGROUND
Hypertension is common, and arterial pressure rhythms are impaired in patients with chronic kidney disease (CKD). Emerging evidence suggests that consideration of excretory function together with proteinuria may provide a more holistic assessment of the extent of derangement in renal function.


METHODS
To evaluate the independent relationships of estimated GFR and proteinuria with the mean level of and the circadian variation in blood pressure, we evaluated 336 patients, 184 (55%) patients with CKD (eGFR <60 or urine protein/creatinine >0.22) and 152 (45%) without CKD.


RESULTS
The mean level of systolic and diastolic BP increased with increasing severity of proteinuria as well as with increasing impairment in GFR. When proteinuria and eGFR were considered together in the same regression model, proteinuria-not eGFR-was related to the severity of hypertension. Non-dipping was present in 52% of those with eGFR >60 and 55% in those with no proteinuria. Non-dipping was seen early in the course of impaired GFR or proteinuria. Adjusted for proteinuria, the odds ratio for non-dipping in those with CKD was 1.71 (95% CI 1.03-2.84, P = 0.036). The odds ratio for non-dipping in those with proteinuria was 1.75 (95% CI 1.00-3.08, P = 0.049) when adjusted for CKD. A cosinor model that evaluates the midline estimating statistic of rhythm (MESOR) and circadian variation revealed that proteinuria was a stronger determinant of MESOR compared to the CKD stage; the CKD stage in addition to proteinuria did not further add to the determination of MESOR. The amplitude of variation was markedly blunted in patients with the earliest stages of derangement in kidney function whether it was assessed by proteinuria or eGFR.


CONCLUSIONS
These results demonstrate a graded relationship of proteinuria and eGFR with the mean level of BP and a non-graded relationship with circadian variation. Consideration of these two simple tests of renal function may better assist in gauging the severity of hypertension in patients with CKD.