Membrane-based pretreatment to mitigate variations in desalination plants.

The main source of potable water in high water-stress areas is commonly produced in brackish and seawater desalination plants. Owing to the presence of high concentration of suspended solids, organic matter and colloidal particles in raw water, pretreatment processes are needed for a stable operation of desalination plants. A submerged membrane ultrafiltration pilot plant has been operated as pretreatment of complex brackish surface water to study the filtration performance. The results show the membrane performance, chemical reagent requirements, water quality and cleaning procedures efficiency of an ultrafiltration pilot plant used as pretreatment for a reverse osmosis system. Alternative chemical cleaning procedures have been satisfactorily implemented, which maximize permeability recovery and allow a stable operation.

Human Secretory IgM Antibodies Activate Human Complement and Offer Protection at Mucosal Surface.

IgM molecules circulate in serum as large polymers, mainly pentamers, which can be transported by the poly-Ig receptor (pIgR) across epithelial cells to mucosal surfaces and released as secretory IgM (SIgM). The mucosal SIgM molecules have non-covalently attached secretory component (SC), which is the extracellular part of pIgR which is cleaved from the epithelial cell membrane. Serum IgM antibodies do not contain SC and have previously been shown to make a conformational change from 'a star' to a 'staple' conformation upon reaction with antigens on a cell surface, enabling them to activate complement. However, it is not clear whether SIgM similarly can induce complement activation. To clarify this issue, we constructed recombinant chimeric (mouse/human) IgM antibodies against hapten 5-iodo-4-hydroxy-3-nitro-phenacetyl (NIP) and in addition studied polyclonal IgM formed after immunization with a meningococcal group B vaccine. The monoclonal and polyclonal IgM molecules were purified by affinity chromatography on a column containing human SC in order to isolate joining-chain (J-chain) containing IgM, followed by addition of excess amounts of soluble SC to create SIgM (IgM J+ SC+). These SIgM preparations were tested for complement activation ability and shown to be nearly as active as the parental IgM J+ molecules. Thus, SIgM may offer protection against pathogens at mucosal surface by complement-mediated cell lysis or by phagocytosis mediated by complement receptors present on effector cells on mucosa.

Treatment and overall survival in renal cell carcinoma: a Swedish population-based study (2000-2008).

BACKGROUND: This retrospective register study assessed overall survival (OS) and influential factors on OS in Swedish renal cell carcinoma (RCC) patients. METHODS: Using three merged national health registers, Cox proportional-hazards analysis was conducted and, in three models, it was used to assess the impact of cytokine (interferon-α and tyrosine kinase inhibitor (TKI; sunitinib or sorafenib) treatment on OS in metastatic (m)RCC. RESULTS: From 2000 to 2008, 8009 patients were diagnosed with RCC and 2753 with mRCC (2002-2008). Median OS in RCC patients diagnosed from 2006 to 2008 compared with 2000-2005 was not reached vs 47.9 months (P<0.001), and in mRCC patients diagnosed from 2006 to 2008 compared with 2002-2005, was 12.4 vs 9.6 months, respectively (P=0.004). Factors associated with significantly improved OS in RCC were female gender, lower age, and previous nephrectomy, and, in mRCC female gender, previous nephrectomy, and any TKI prescription (Model 1: median-adjusted OS, 19.4 months (TKI patients) vs 9.7 months (non-TKI patients); hazard ratio, 0.621; P<0.001). CONCLUSION: OS was improved in Swedish patients diagnosed with RCC and mRCC in the period 2006-2008 compared with 2000-2005 (RCC) and 2002-2005 (mRCC). Although multifactorial in origin, results suggest that increased nephrectomy rates and the use of TKIs contributed to the improvement seen in mRCC patients.

Matching-adjusted indirect treatment comparison of the efficacy of enzalutamide versus apalutamide for the treatment of nonmetastatic castration-resistant prostate cancer.

BACKGROUND: To date, the efficacy of the androgen receptor inhibitors enzalutamide and apalutamide for the treatment of nonmetastatic castration-resistant prostate cancer (nmCRPC) has not been compared directly in a clinical trial setting. Indirect comparisons can be used to assess relative efficacy and provide important information to guide treatment decisions. PROSPER and SPARTAN were double-blind, randomized, placebo-controlled, phase III trials in patients with nmCRPC with overall similar study designs and inclusion and exclusion criteria. Using an anchored matching-adjusted indirect comparison, based on the final data from the PROSPER and SPARTAN studies, we assessed the comparative efficacy of enzalutamide and apalutamide, both plus androgen deprivation therapy. METHODS: Using placebo as the common comparator, individual patient data from PROSPER were matched to the aggregate patient data from SPARTAN and efficacy endpoints from PROSPER were re-weighted accordingly. Patient baseline characteristics and endpoints were clinically and statistically tested to identify potential effect modifiers, according to National Institute for Health and Care Excellence guidelines. Hazard ratios for overall survival (OS), metastasis-free survival (MFS), and time to chemotherapy (TTCx) were re-estimated for PROSPER using weighted Cox proportional hazards models and indirectly compared with those of SPARTAN using a Bayesian network meta-analysis. RESULTS: Estimated hazard ratios [95% credible interval (CrI)] for enzalutamide versus apalutamide were 0.80 (95% CrI 0.58-1.10) for OS, 0.94 (95% CrI 0.69-1.29) for MFS2, and 0.90 (95% CrI 0.63-1.29) for TTCx. Similar results were seen for sensitivity analyses conducted for OS and MFS. Bayesian probability analyses showed a 91.7% favoring enzalutamide for OS, 65.1% for MFS, and 71.4% for TTCx. CONCLUSIONS: The results of this matching-adjusted indirect comparison of final data from PROSPER and SPARTAN indicate comparable efficacy of enzalutamide and apalutamide with potentially a greater probability of longer MFS, OS, and TTCx in patients with nmCRPC treated with enzalutamide versus apalutamide.

Structural difference in the complement activation site of human IgG1 and IgG3.

The C1q binding epicentre on IgG molecules involves residues Asp(270), Lys(322), Pro(329) and Pro(331) in the C(H)2 domain. IgG1 and IgG3 are usually the most efficient of the four human IgG subclasses in activating complement and they both share all these residues. To reveal possible differences in the structural requirement for complement activation, we created a number of NIP (5-iodo-4-hydroxy-3-nitro-phenacetyl) specific IgG1 and IgG3 antibodies with parallel mutations in or near the putative C1q binding site. The mutants were tested simultaneously for antibody induced, antibody-dependent complement-mediated lysis (ADCML) at high and low antigen concentration on the target cells using sera of human, rabbit and guinea pig as complement source. In addition, we tested the antibodies against target cells decorated with the NP hapten, which has 10-fold lower affinity for the antibodies compared to the NIP hapten. We also used ELISA methods to measure complement activation. We observed a clear difference between IgG1 and IgG3 localized to residues Asp(270), Leu(334), Leu(335). For all these residues, and especially for Asp(270), IgG1 was heavily reduced in complement activation, while IgG3 was only moderated reduced, by alanine substitution. This difference was independent of the long hinge region of IgG3, demonstrated by hinge region truncation of this isotype such that it resembles that of IgG1. This report indicates the presence of structural differences between human IgG1 and IgG3 in the C1q binding site, and points to a specialization of the two isotypes with respect to complement activation.

Intraoperative dreams reported after general anaesthesia are not early interpretations of delayed awareness.

BACKGROUND: Dreams are more frequently reported than awareness after surgery. We define awareness as explicit recall of real intraoperative events during anaesthesia. The importance of intraoperative dreaming is poorly understood. This study was performed to evaluate whether intraoperative dreams can be associated with, or precede, awareness. We also studied whether dreams can be related to case-specific parameters. METHODS: A cohort of 6991 prospectively included patients given inhalational anaesthesia were interviewed for dreams and awareness at three occasions; before they left the post-anaesthesia care unit, days 1-3 and days 7-14 after the operation. Uni- and multivariate statistical relations between dreams, awareness and case-specific parameters were assessed. RESULTS: Two hundred and thirty-two of 6991 patients (3.3%) reported a dream. Four of those also reported awareness and remembered real events that were distinguishable from their dream. Awareness was 19 times more common among patients who after surgery reported a dream [1.7% vs. 0.09%; odds ratio (OR) 18.7; P=0.000007], but memories of dreams did not precede memories of awareness in any of the 232 patients reporting a dream. Unpleasant dreams were significantly more common when thiopentone was used compared with propofol (OR 2.22; P=0.005). Neutral or pleasant dreams were related to lower body mass index, female gender and shorter duration of anaesthesia. CONCLUSIONS: We found a statistically significant association between dreams reported after general anaesthesia and awareness, although intraoperative dreams were not an early interpretation of delayed awareness in any case. A typical dreamer in this study is a lean female having a short procedure.

BIS does not predict dreams reported after anaesthesia.

BACKGROUND: In earlier studies, between 1% and 57% of patients have been reported to dream during anaesthesia. Thus, dreaming is much more common than definite memories of real events. We wanted to examine whether dreaming during anaesthesia is related to insufficient hypnotic action, as indicated by BIS levels and, thus, may constitute a risk for awareness. METHODS: After IRB approval, 2653 consecutive surgical patients were included. BIS registrations were recorded continuously during the anaesthetic procedure. The patients were interviewed on three occasions after anaesthesia. Standard questions, according to Brice, to evaluate awareness and dreaming during anaesthesia were asked. The dreams were categorized as either pleasant/neutral or unpleasant without any further evaluation of the dream content. Episodes with a mean BIS below 40, above 60 and above 70 were identified and subdivided according to duration (1, 2, 4 and 6 min, respectively). The total time as well as number and duration of episodes for the three BIS-levels were used to analyze any relation to reported dreaming. The mean BIS was also analyzed. RESULTS: Dreaming during anaesthesia was reported by 211 of patients (8.0%) on at least one of the post-operative interviews. BIS data did not show any significant correlation with dreaming, and neither did any of the tested case-specific parameters (gender, age, ASA group, BMI, use of relaxants, induction agent, maintenance agent, length of procedure, omitting N(2)O and concomitant regional anaesthesia). CONCLUSION: Dreaming during anaesthesia seems to be a separate phenomenon, not in general related to insufficient anaesthesia as indicated by high BIS levels.

Bispectral index monitoring: appreciated but does not affect drug dosing and hypnotic levels.

BACKGROUND: Bispectral index (BIS) has been associated with benefits from less-deep anesthesia as well as preventing awareness, albeit not at the same time. We investigated how increasing experience from BIS in clinical practice affect the hypnotic level, drug consumption, as well as subjective opinions on this monitoring. METHODS: Eight certified registered nurse anesthetists (CRNAs) with previous experience from 88 (46-121) BIS monitored cases anesthetized 80 cases with concealed BIS, followed by 80 cases with available BIS. Additional education and training was followed by yet another 160 patients randomized to open or blindly recorded BIS. BIS levels, anesthetic gas consumption, fentanyl use, and subjective opinions on utility and reliability were investigated. RESULTS: After gaining initial experience from BIS monitoring, the fraction of time with BIS levels of 40-60 did not deteriorate in cases with concealed monitoring and no further improvement was found in subsequent cases with available data from the BIS monitoring, not even after additional training and encouragement to adhere to the 40-60 interval. Compared with the first experience from BIS monitoring the subjective opinions on utility had increased from 33 to 78 mm (100 mm visual analog scales) (P<0.0001). CONCLUSION: Although BIS became considerably appreciated, growing experience and repeated education had no impact on drug dosing and BIS levels.

Valganciclovir is safe and effective as pre-emptive therapy for CMV infection in allogeneic hematopoietic stem cell transplantation.

Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection continues to be an important cause of morbidity and mortality in the hematopoietic stem cell transplant (HSCT) recipient. The standard drug for pre-emptive therapy is intravenous ganciclovir (GCV). Valganciclovir (VGC), the oral pro-drug of GCV, has excellent bioavailability and is ideal for oral therapy. Since March 2002, VGC was adopted in our center for outpatient pre-emptive therapy in all patients undergoing allogeneic HSCT. Fifty-two allogeneic HSCT recipients were followed weekly via Digene hybrid capture assay. Patients with a positive assay were treated with VGC 900 mg p.o. b.i.d. x 14 days followed by 900 mg p.o. QD until at least 7 days after a negative test. Eighteen patients (14 sib, four MUD) had 30 episodes of CMV DNA detection treated with oral VGC. Median duration of therapy was 21 days (range 10-21 days). The rate of response was 93% (28/30) as confirmed by a negative assay within 14 days. No significant toxicity was encountered. Two patients failed oral VGC. One case of CMV enteritis was diagnosed in a patient with acute GVHD. Pre-emptive therapy of CMV infection with oral VGC is safe and effective in allogeneic HSCT recipients.

Outcome after awareness with explicit recall.

Between 0.1% and 0.2% of surgical patients given general anesthesia remember having been aware during the procedure. Not all, but some of these patients have experienced pain, anxiety or both while being aware. In addition, there is a risk for developing anxiety symptoms. These symptoms can constitute a posttraumatic stress syndrome or parts thereof. The anxiety symptoms may be transient, but can persist in some patients. The majority of available studies on suffering due to awareness are retrospective, and potential selection bias in the studied cohorts should be considered when the likelihood for negative experiences of awareness are discussed.

Human IgG3 can adopt the disulfide bond pattern characteristic for IgG1 without resembling it in complement mediated cell lysis.

In this paper we describe the construction of mouse-human IgG3 mutant antibodies resembling IgG1 in their disulfide bond pattern between the heavy and light chain (H-L) and between the two heavy chains (H-H). The effector functions of these mutant antibodies were compared to normal IgG3 and IgG1. Changing only the disulfide bond pattern between the heavy and light chains did not alter the ability to induce complement mediated cell lysis (CML), regardless of the amount of corresponding antigen that had been introduced to the surface of the target cells. However, alteration of the disulfide bond pattern between the two heavy chains had a large effect on CML due to shortening of the hinge from 62 to 15 amino acids. No difference between the mutants and normal antibodies in antibody-dependent cell-mediated cytotoxicity (ADCC) was observed. This suggests that IgG3 can adopt the H-L disulfide bond pattern of IgG1 without obtaining the CML activity characteristic for IgG1.

Some biological properties of the impure dichloride salt of tetrakis[p-(dimethylamino)phenyl]ethylene and a pinacolone.

The impure dichloride salt of tetrakis[p-(dimethylamino)phenyl]ethylene and a pinacolone that is a substituted acetophenone show several biological properties, one of which is activity against lymphosarcoma in mice. The involvement, if any, of free radicals in the biological properties of these substances is discussed.

Cardiac myocytes and dendritic cells harbor human immunodeficiency virus in infected patients with and without cardiac dysfunction: detection by multiplex, nested, polymerase chain reaction in individually microdissected cells from right ventricular endomyocardial biopsy tissue.

Two hundred fifteen patients infected with human immunodeficiency virus (HIV) participated in a prospective longitudinal study of HIV-related heart disease. Evaluation included signal-averaged electrocardiography and echocardiography. Fifteen patients underwent endomyocardial biopsy, 5 had cardiovascular symptoms and 10 did not. Cardiac myocytes or dendritic cells were prepared by individual cell microdissection to sort them from other cell types such as interstitial cells or circulating blood elements. HIV proviral sequences were amplified in samples of 15 to 20 cells of each type by multiplex, nested, polymerase chain reaction and hybridized to 32P-labeled probes specific for regions within the gag and pol genes of HIV-1. The results showed the presence of HIV sequences in myocytes of 2 of 5 patients with cardiac symptoms and in 6 of 10 without. Thus, symptomatic HIV cardiomyopathy did not appear to be a direct consequence of the virus on myocardial cells. In dendritic cells, HIV sequences were detected in 5 of 5 patients with cardiac symptoms and in 8 of 10 with apparently normal ventricular function. Furthermore, dendritic cells were somewhat more numerous in the myocardium of symptomatic than asymptomatic patients. Our studies are the first to directly detect the HIV genome in purified cardiac myocytes from patients with and without cardiac dysfunction. Our findings do not support a direct role of the virus in myocardial dysfunction. However, the results do suggest that the interstitial dendritic cells may be involved in some manner in the development of cardiac dysfunction observed in HIV-infected patients.

The detection of airborne Mycobacterium tuberculosis using micropore membrane air sampling and polymerase chain reaction.

STUDY OBJECTIVES: Mycobacterium tuberculosis (MTb) bacilli are carried on airborne droplet nuclei produced by aerosolization that can occur from coughing, talking, or even singing. Because of their prolonged period of suspension, they can be filtered from the air onto a porous medium and readily detected using polymerase chain reaction (PCR). DESIGN: Prospective cohort analysis. SETTING: Samples of circulating air were collected over a 12-month period from within the rooms of 10 hospitalized patients who were under respiratory isolation to rule out MTb infection. A small laboratory pump was used to draw ambient air at a rate of 2 L/min over a 6-h period through a 0.2-microm polycarbonate membrane filter placed near the patient's bed. Analysis of the membrane filters was conducted using PCR. Sputum cultures for MTb were performed simultaneously, and the results of smears stained for acid-fast bacilli (AFB) were noted. MEASUREMENTS AND RESULTS: MTb complex was successfully detected by PCR in six of seven patients in whom sputum MTb cultures were subsequently positive, and in zero of three with subsequently negative sputum cultures. Sampling in one patient with a positive culture, in whom PCR results were negative, was only carried out for 2 h due to pump malfunction. One of the six PCR-positive patients was AFB-smear negative at the time of air sampling. CONCLUSIONS: Our preliminary findings indicate that the technique of Micropore membrane air sampling with PCR analysis has important applications in the epidemiology and diagnosis of MTb.

Primary cutaneous aspergillosis: case report and review of the literature.

Primary cutaneous aspergillosis is an uncommon entity that may occur in immunosuppressed hosts, usually resulting from contact with contaminated medical devices used in patient care. The infection spreads locally with subsequent skin necrosis due to angioinvasion and thrombosis. We report primary cutaneous aspergillosis following contact with contaminated gauze, and we review the relevant literature.

Unpredictability of commercially available exoantigen culture confirmation tests in confirming the identity of five Blastomyces dermatitidis isolates.

Colonial and microscopic features of five fungal isolates from three patients suggested Blastomyces dermatitidis. Extracts from the mold forms of all isolates were tested on several occasions with commercially available Exoantigen immunodiffusion culture-confirmation test reagents and Nolan reagents. All three isolates from patient 1 were negative on four separate attempts with Exoantigen reagents using conventional ("slant") and "broth" extraction methods, and were also negative on one attempt with the Nolan reagents. The isolate from patient 3 was negative on three attempts using both reagent kits. The isolate from patient 2 was negative on four of five attempts with Exoantigen test reagents and positive on one attempt with Nolan reagents. Commercially prepared chemiluminescence-labeled DNA probes (Gen-Probe, San Diego, CA) directed at ribosomal RNA from B. dermatitidis and Histoplasma capsulatum confirmed all five isolates as B. dermatitidis. The cost and labor of the exoantigen and DNA Probe culture confirmation tests were evaluated. New methods for confirming the identity of cultural isolates of B. dermatitidis that are sensitive, specific, and commercially available are greatly needed.

Special considerations for the clinical microbiology laboratory in the diagnosis of infections in the cancer patient.

The clinical microbiology laboratory faces enormous challenges in diagnosing infections that cause morbidity and mortality in cancer patients. Such laboratories face several issues that surpass those faced by laboratories that perform more routine work. Issues such as sources of clinical specimens, need for correlation and interaction between laboratory and clinical services, blood cultures, susceptibility testing, and the role of new molecular diagnostic techniques are considered in this article.

Comparison of vidas Clostridium difficile toxin-A assay and premier C. difficile toxin-A assay to cytotoxin-B tissue culture assay for the detection of toxins of C. difficile.

Damage to the intestinal mucosa by Clostridium difficile (CD) is toxin mediated. Two enzyme immunoassays (EIAs) for toxin-A detection, the automated Vitek immunodiagnostic assay system CDA (Vidas CDA), and the Premier toxin A (Premier) were tested for their ability to detect toxin A in 301 stool samples and compared with an in-house tissue culture assay for toxin B (TCA). Of these 301 samples, 49 were TCA positive and 252 were TCA negative. Agreement between Vidas CDA and TCA on the initial run was 85% (255 of 301) and increased to 94% (278 of 296) when discordant samples were retested from available frozen specimens. Corresponding levels of agreement for Premier were 91% (272 of 301) and 98% (284 of 288), respectively. If tissue culture positivity at any titer was used as the sole criterion for positivity of the specimen, agreement with positive TCA before and after repeat testing was 57% (26 of 49) and 74% (34 of 46) for Vidas CDA and 65% (32 of 49) and 95% (36 of 38) for Premier. Agreement with negative TCA titers was good: 90% for Vidas CDA and 95% for Premier, and 98% for Vidas CDA and 99% for Premier after repeat testing. Predictive values positive and negative after repeat testing were, respectively, 88% and 96% for Vidas CDA, and 95% and 99% for Premier. Results for the automated and manual EIA methods for detection of C. difficile toxin A were obtained in 2.5 h as compared with 36-48 h for tissue culture.

Aberrant Histoplasma capsulatum. Confirmation of identity by a chemiluminescence-labeled DNA probe.

A cottony, light tan, filamentous fungus with pear-shaped microconidia and lacking tuberculated macroconidia was isolated from a bronchial lavage specimen. Subculture on several media at 37 degrees C failed to convert the fungus to a yeast form after several weeks; attempts at in vivo conversion in mice were also unsuccessful. Sera obtained several months apart showed M bands with Histoplasma capsulatum (HC) antigen by immunodiffusion and an increase in complement fixation titers with mycelial and yeast phase antigens of HC. Parallel identity was obtained on two occasions with exoantigen culture confirmation reagents for HC from Immuno-Mycologics as well as one of identity with Nolan reagents. Extracts from four Chrysosporium spp. strains had no identity reactions with HC with either kit. The fungus was identified as HC by the Accuprobe Histoplasma chemiluminescence-labeled DNA probe directed at ribosomal RNA, whereas all four Chrysosporium spp. isolates tested negative. DNA probes are a fast and accurate method to confirm the identity of aberrant fungal isolates.