20354418
Clinical significance of hyperattenuating mucoid impaction in allergic bronchopulmonary aspergillosis: an analysis of 155 patients.
BACKGROUND
Allergic bronchopulmonary aspergillosis (ABPA) is a disease that presents with diverse clinicoradiologic manifestations. High-attenuation mucus (HAM) is a characteristic radiologic finding seen in patients with ABPA; however, the clinical significance of the entity remains unknown.


AIMS AND OBJECTIVES
To describe the outcome of patients with ABPA who were demonstrated to have HAM, and compare with the outcome of patients without HAM.


METHODS
All consecutive patients with asthma presenting to the Chest Clinic of this institute over a 4-year period were screened with an Aspergillus skin test. Patients with positive findings were further investigated, and the diagnosis of ABPA was confirmed based on predefined criteria. The patients were further classified into two groups based on the presence of HAM on HRCT scan.


RESULTS
During the study period, 755 patients were screened for ABPA using the Aspergillus skin test; 291 patients (38.5%) had positive findings, and ABPA was diagnosed in 155 patients (mean age, 33.98 years; 76 women). Twenty-nine patients (18.7%) with ABPA were identified to have HAM on HRCT scans at presentation. The baseline characteristics were similar between the two groups, but patients with HAM had higher mean eosinophil counts, higher mean serum total IgE, and higher Aspergillus fumigatus-specific IgE levels. On multivariate analysis, both the severity of bronchiectasis and HAM predicted relapse of ABPA (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.13 to 1.42; and OR, 3.61; 95% CI, 1.23 to 10.61, respectively). Failure to achieve complete remission was influenced by the severity of bronchiectasis but not by HAM (OR, 1.55; 95% CI, 1.29 to 1.85; and OR, 3.41; 95% CI, 0.89 to 13.1, respectively).


CONCLUSIONS
HAM impaction in ABPA is associated with initial serologic severity and frequent relapses but does not seem to influence complete remission.
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.
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.
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.
45999589
Noninvasive ventilation in acute heart failure.
12010523
What are high-flow and low-flow oxygen delivery systems?
To the Editor:

We read with interest the article, “A Pilot Study of Normobaric Oxygen Therapy in Acute Ischemic Stroke.”1 However, we have certain reservations with the terminology and the method of oxygen delivery used by the authors.

First, regarding the terminology of “high-flow” oxygen used by the authors, the authors mention the flow rates but not the oxygen delivery system used. An oxygen delivery system is a device used to administer, regulate, and supplement oxygen to a subject to increase the arterial oxygenation. In general, the system entrains oxygen and air to prepare a fixed concentration required for administration. Oxygen delivery systems are generally classified as low-flow or variable-performance devices and high-flow or fixed-performance devices.2 Low-flow systems provide oxygen at …
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.
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.
38466120
Novel therapeutic agents in ovarian cancer.
AIMS
Epithelial ovarian cancer is responsible for 4% of all cancer deaths in women, and the five-year overall survival of patients with advanced disease is 30-40%. Treatment currently comprises a combination of surgery and chemotherapy with carboplatin and paclitaxel. The main reason for treatment failure is that the majority of patients present with advanced disease, and current drugs are unable to effect a cure even in chemosensitive patients. This article systematically reviews novel therapeutic strategies that have been evaluated in patients with ovarian cancer in the last 5 years.


METHODS
Pubmed (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?DB=pubmed) and American Society of Clinical Oncology Annual conference abstracts were searched using the terms "(phase I OR phase II OR phase III OR phase 1 OR phase 2 OR phase 3) AND (ovary OR ovarian) AND (cancer OR carcinoma)" from January 2000 to May 2005 to identify studies for potential inclusion in this review. Reviews of novel therapies in ovarian cancer were also used to identify additional clinical trials.


FINDINGS
A wide range of therapeutic strategies are currently being evaluated in ovarian cancer. These include novel cytotoxics, small molecule inhibitors, monoclonal antibodies, gene therapy and immuno-therapy strategies. The rationale for the development of these agents includes enhancement of efficacy by targeting novel biological pathways, re-sensitisation to existing drugs, simplification of drug administration and/or reduction of drug-toxicity.


CONCLUSIONS
Current developments have the potential to result in substantial improvements in the outlook for women with ovarian cancer.
20955522
Ovarian cancer: strategies for overcoming resistance to chemotherapy
Ovarian cancer is responsible for 4% of deaths from cancer in women. Treatment comprises a combination of surgery and chemotherapy, but patients typically experience disease relapse within 2 years of the initial treatment. Further treatment can extend survival, although relapse eventually occurs again. A better understanding of the mechanisms that underlie this drug resistance should allow treatment to be optimized, so that substantial improvements in the outlook for women with this disease can be achieved.
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.