11307916
Clinical significance of decline in serum IgE levels in allergic bronchopulmonary aspergillosis.
BACKGROUND AND AIMS
The total serum IgE level is a marker of immunological activity in allergic bronchopulmonary aspergillosis (ABPA), and a 35% decline beyond six weeks is traditionally taken as criteria for remission. The aim of this study was to evaluate the magnitude and clinical significance of decline in serum IgE levels at six weeks in patients with ABPA.


METHODS
All consecutive patients with ABPA presenting to the Chest Clinic were followed up with clinical evaluation, total IgE levels and chest x-ray every six weeks for three months. We analyzed the percentage decline in IgE levels and correlated it with clinical outcomes of relapse and complete remission.


RESULTS
Of the 242 asthmatics, 54 were diagnosed with ABPA (29 males, 25 females; mean age-34 years). There was clinical and radiological improvement at six weeks in all patients receiving glucocorticoid therapy. The IgE levels fell by a mean of 38.8%, and the decline was significantly higher in patients with baseline IgE levels >2500IU/mL than with levels <or=2500IU/mL (44% vs. 26%). Twenty-two patients did not attain a 35% decline in IgE levels, and this number was significantly higher in patients with IgE levels <2500IU/mL. On multivariate analysis, the decline in IgE levels at six weeks did not predict clinical outcomes.


CONCLUSIONS
A 35% decline in serum IgE levels at six weeks is not seen in all patients with ABPA, and the decline is slower in patients with baseline IgE levels <2500IU/mL. The quantum decline in serum IgE levels does not predict clinical outcomes.
45999589
Noninvasive ventilation in acute heart failure.
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.
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
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.
5428839
Blood pressure components and the risk for end-stage renal disease and death in chronic kidney disease.
BACKGROUND AND OBJECTIVES
Mean arterial pressure has been used in clinical trials in nephrology to randomly assign and treat patients, yet the pulsatile component of BP is recognized to influence outcomes in older people. I examined the unique contributions of systolic (SBP) and diastolic BP (DBP) on the risk for ESRD and death in patients with chronic kidney disease (CKD).


DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
A single-center, prospective cohort study was conducted of 218 veterans with CKD (22% black, 4% women, mean age 68 yr, clinic BP 154.1 +/- 25.1/85.2 +/- 13.9 mmHg, 48% with diabetes).


RESULTS
During follow-up of up to 7 yr, 63 patients had ESRD and 102 patients died. Compared with those with controlled SBP (<130 mmHg), patients with moderate control (130 to 149 mmHg) had hazard ratio of 3.87 and those with poor control hazard ratio of 9.09 for ESRD. DBP had no direct ability to predict ESRD. For all-cause mortality, a J-shaped relationship was seen for SBP and an inverse relationship was seen for DBP. Considered jointly in the Cox model, a higher SBP and lower DBP improved the prediction of all-cause mortality compared with either BP component alone. The presence of J curve was especially pronounced in patients with advanced CKD, absence of clinical proteinuria, or age >65 yr.


CONCLUSIONS
In older patients with CKD, SBP predicts ESRD and a higher SBP and lower DBP predicts all-cause mortality. Lower BP of <110/70 mmHg is a marker of higher mortality in older individuals with advanced CKD.
39974976
Antiproteinuric effect of oral paricalcitol in chronic kidney disease.
BACKGROUND
Proteinuria is a marker of cardiovascular and renal disease in patients with chronic kidney disease (CKD), and reduction in proteinuria has been associated with improved cardiovascular and renal outcomes. While active vitamin D and its analogs have been shown to have renal protective effects in animals, these hormones have not been shown to reduce proteinuria in CKD patients.


METHODS
In three double-blind, randomized, placebo-controlled studies to evaluate the safety and efficacy of oral paricalcitol, 220 CKD stage 3 and 4 patients with secondary hyperparathyroidism (SHPT) were randomized to oral paricalcitol (N= 107, mean dose 9.5 microg/week) or placebo (N= 113) and followed for up to 24 weeks. In conjunction with other safety measures, proteinuria was measured by dipstick and read by an automated reader at the beginning and end of trial. We subsequently analyzed the dipstick data to evaluate the effect of paricalcitol on proteinuria.


RESULTS
At baseline, proteinuria was present in 57 patients randomized to oral paricalcitol and 61 patients randomized to placebo (NS). At the final visit, 29/57 (51%) of the paricalcitol patients compared to 15/61 (25%) placebo patients had reduction in proteinuria, P= 0.004 (odds for reduction in proteinuria 3.2 times greater for paricalcitol patients, 95% CI 1.5-6.9). For the patients who had both proteinuria at baseline and parathyroid hormone (PTH) suppression (end point defined as 2 consecutive > or =30% decreases in iPTH from baseline), 27/51 (53%) patients had a reduction in the proteinuria in the paricalcitol group and 0/7 (0%) had a reduction in proteinuria in the placebo group. Reduction of proteinuria favored patients on paricalcitol, regardless of age, sex, race, diabetes mellitus, hypertension, or use of therapies to block the renin-angiotensin-aldosterone system (RAAS).


CONCLUSION
Our results demonstrate that the reduction in proteinuria was associated with paricalcitol treatment, and the reduction in proteinuria was independent of concomitant use of agents that block the RAAS. Paricalcitol as a potential pharmacologic means of reducing proteinuria in CKD patients warrants further investigation.
30308813
Strategies and feasibility of hypertension control in a prevalent hemodialysis cohort.
BACKGROUND
There are few data to demonstrate the feasibility of long-term blood pressure (BP) control using short dialysis sessions as practiced in the US. Control of hypertension in hemodialysis patients may reduce the risk of cardiovascular events.


METHODS
Forty-two dialysis patients had BPs and weights recorded before and after dialysis for two consecutive weeks and were followed by one physician over three years. Patients were treated by ultrafiltration and conventional antihypertensive drugs and BPs were repeated at three years in the 32 survivors.


RESULTS
93% of the patients (39/42) were African-American. At inception, 85% of the patients were hypertensive with BPs of 154 +/- 23/83 +/- 14 mmHg and 137 +/- 22/74 +/- 14 mmHg pre- and post-dialysis, respectively. The response to ultrafiltration was dependent upon gender, with women having a greater BP reduction compared to men. At three-year follow-up, the BP had dropped significantly in the survivors a mean of 9.4/6.7 mmHg. Pre- and post-dialysis weights, post dialysis BP and interdialytic weight-gain were unchanged. The BP reduction was achieved by an increase in the number of antihypertensive medications from 0.91 +/- 0.86 medications to 1.41 +/- 1.16. Improved BP control did not worsen the efficiency of dialysis (Kt/V). The use of beta-blockers doubled during the period of follow-up. Compared to the USRDS average cardiovascular death rate, the risk of cardiovascular deaths was improved 80% over three years.


CONCLUSION
Long-term BP reduction can be achieved through the use of antihypertensive agents and volume control in a predominantly African-American hemodialysis population. This may impact cardiovascular mortality.
30954752
Salt, salt sensitivity, and the endothelium: a pathway to discovery of molecular mechanisms.
See related article, pp 951–956

This issue of Hypertension contains a report of molecular mechanisms transducing dietary salt intake1 that may have broad clinical relevance. These molecular mechanisms are complex, but to begin to understand this study we have to understand the importance of dietary salt intake and salt sensitivity. This background will be discussed in some detail before discussing the molecular mechanisms.

Although cohort studies have called into question the role of dietary salt intake in causing hypertension,2 cause and effect relationships are most convincing when demonstrated using randomized clinical trials. It would be unethical to perform a randomized clinical trial in which the dietary intake of salt (sodium chloride) is increased for years in humans to observe an increase in blood pressure. However, such an experiment in primates has been performed by Denton et al,3 who studied in Gabon, Africa, 26 chimpanzees. Chimpanzees have a native diet that is vegetarian and is very high in potassium content. The baseline sodium intake in these primates was only 6 mEq/d; in contrast, that of K was 235 mEq/d. Blood pressure was measured in the 26 animals for 1 year. Subsequently, among half the animals, increasing amounts of salt (in increments of 5 g/d sodium) were added to a diet to a steady-state level of 15 g/d. This dietary intake was maintained for 16 months. After this period of dietary supplementation, the diet was switched to baseline and observations made for another 6 months. A dose–response relationship between salt supplementation and blood pressure increment was seen. With 15 g/d sodium supplementation for 67 weeks, the change from baseline in blood pressure was 33/10 mm Hg. In comparison, 5 g/d sodium supplementation for 19 weeks provoked blood pressure change of 12/0 mm Hg. Notably, plasma renin activity was reduced with salt …
12841382
Mode of VAMP substrate recognition and inhibition of Clostridium botulinum neurotoxin F
Clostridium botulinum neurotoxins (BoNTs) cleave neuronal proteins responsible for neurotransmitter release, causing the neuroparalytic disease botulism. BoNT serotypes B, D, F and G cleave and inactivate vesicle-associated membrane protein (VAMP), each at a unique peptide bond. The specificity of BoNTs depends on the mode of substrate recognition. We have investigated the mechanism of substrate recognition of BoNT F by determining the crystal structures of its complex with two substrate-based inhibitors, VAMP 22-58/Gln58D-cysteine and 27-58/Gln58D-cysteine. The inhibitors bind to BoNT F in the canonical direction (as seen for BoNTs A and E substrates) but are positioned specifically via three major exosites away from the active site. The cysteine sulfur of the inhibitors interacts with the zinc and exists as sulfinic acid in the inhibitor VAMP 27-58/Gln58D-cysteine. Arg133 and Arg171, which form part of two separate exosites, are crucial for substrate binding and catalysis.