Risk factors for early mortality in patients with pulmonary tuberculosis admitted to the emergency room.

BACKGROUND AND OBJECTIVES: Mortality of patients with pulmonary tuberculosis (TB) admitted to emergency departments is high. This study was aimed at analysing the risk factors associated with early mortality and designing a risk score based on simple parameters. METHODS: This prospective case-control study enrolled patients admitted to the emergency department of a referral TB hospital. Clinical, radiological, biochemical and microbiological risk factors associated with death were compared among patients dying within one week from admission (cases) and those surviving (controls). RESULTS: Forty-nine of 250 patients (19.6%) experienced early mortality. Multiple logistic regression analysis showed that oxygen saturation (SaO2) ≤90%, severe malnutrition, tachypnoea, tachycardia, hypotension, advanced disease at chest radiography, severe anaemia, hyponatremia, hypoproteinemia and hypercapnia were independently and significantly associated with early mortality. A clinical scoring system was further designed to stratify the risk of death by selecting five simple parameters (SpO2 ≤ 90%, tachypnoea, hypotension, advanced disease at chest radiography and tachycardia). This model predicted early mortality with a positive predictive value of 94.88% and a negative predictive value of 19.90%. CONCLUSIONS: The scoring system based on simple parameters may help to refer severely ill patients early to a higher level to reduce mortality, improve success rates, minimise the need for pulmonary rehabilitation and prevent post-treatment sequelae.

A novel leaf rust resistance gene introgressed from Aegilops markgrafii maps on chromosome arm 2AS of wheat.

KEY MESSAGE: A novel leaf rust resistance gene, LrM, introgressed from Aegilops markgrafii and mapped on chromosome 2AS using SSR- and SNP-based PCR markers will aid in broadening the genetic base of rust resistance in wheat. A new leaf rust resistance gene tentatively named LrM was introgressed from the diploid non-progenitor species Ae. markgrafii (2n = 2x = 14, genome CC) into common wheat using the nulli-5B mechanism. The introgression line ER9-700 showed a high degree of resistance against a wide spectrum of Puccinia triticina pathotypes. Genetic analysis was performed using the F1, F2, F2:3 and BC1F1 generations derived from the cross ER9-700/Agra Local. The results showed a single dominant gene for leaf rust resistance. The resistance gene LrM was mapped on chromosome arm 2AS using SSR- and SNP-based PCR markers. Preliminary mapping with SSR markers in the F2:3 population from the cross ER9-700/Agra Local identified two SSR markers flanking the LrM. SNPs were identified in the genomic region flanked by SSR markers, and SNP-based PCR markers were developed to construct the final map. Three SNP-based PCR markers co-segregated and mapped closest to the resistance gene at a distance of 2 cM. The gene LrM was distinguished from all the other genes designated and mapped on chromosome arm 2AS by molecular markers and rust reaction. All five markers used in the mapping amplified identical alleles in the donor Ae. markgrafii accession and introgression line ER9-700. The chromosomal location and rust reaction suggest that LrM is a novel leaf rust resistance gene that may be useful in broadening the genetic base of leaf rust resistance in wheat.

An unusual case of Aspergillus endocarditis of native aortic valve following ECMO.

Fungal endocarditis following Extracorporeal membrane oxygenation (ECMO) is rare and very rarely reported. Though rare it has a high mortality rate. A 49-year-old male patient who had venovenous ECMO presented with aortic valve endocarditis after 40 days. He underwent sutureless bioprosthehtic valve placement and debridement of abscess. Abscess fluid grew aspergillus species and was started on dual antifungal intravenous amphotericin and variconazole. He was discharged after 1 month with oral variconazole. Incidence of aseptic endocarditis (AE) has been on rise due to increase in invasive procedures. Blood culture is mostly sterile, and fever may be absent. Abscess debridement and aggressive dual antifungal treatment helped our patient in his road to recovery. In current era with increasing use of ECMO, newer rarer complications should be kept in mind. High index of suspicion is required for diagnosing fungal endocarditis after ECMO.

Integration of real-time internal electromagnetic position monitoring coupled with dynamic multileaf collimator tracking: an intensity-modulated radiation therapy feasibility study.

PURPOSE: Continuous tumor position measurement coupled with a tumor tracking system would result in a highly accurate radiation therapy system. Previous internal position monitoring systems have been limited by fluoroscopic radiation dose and low delivery efficiency. We aimed to incorporate a continuous, electromagnetic, three-dimensional position tracking system (Calypso 4D Localization System) with a dynamic multileaf collimator (DMLC)-based dose delivery system. METHODS AND MATERIALS: A research version of the Calypso System provided real-time position of three Beacon transponders. These real-time three-dimensional positions were sent to research MLC controller with a motion-tracking algorithm that changed the planned leaf sequence. Electromagnetic transponders were embedded in a solid water film phantom that moved with patient lung trajectories while being irradiated with two different plans: a step-and-shoot intensity-modulated radiation therapy (S-IMRT) field and a dynamic IMRT (D-IMRT) field. Dosimetric results were recorded under three conditions: no intervention, DMLC tracking, and a spatial gating system. RESULTS: Dosimetric accuracy was comparable for gating and DMLC tracking. Failure rates for gating/DMLC tracking are as follows: +/-3 cGy 10.9/ 7.5% for S-IMRT, 3.3/7.2% for D-IMRT; gamma (3mm/3%) 0.2/1.2% for S-IMRT, 0.2/0.2% for D-IMRT. DMLC tracking proved to be as efficient as standard delivery, with a two- to fivefold efficiency increase over gating. CONCLUSIONS: Real-time target position information was successfully integrated into a DMLC effector system to modify dose delivery. Experimental results show both comparable dosimetric accuracy as well as improved efficiency compared with spatial gating.

Toward submillimeter accuracy in the management of intrafraction motion: the integration of real-time internal position monitoring and multileaf collimator target tracking.

PURPOSE: We report on an integrated system for real-time adaptive radiation delivery to moving tumors. The system combines two promising technologies-three-dimensional internal position monitoring using implanted electromagnetically excitable transponders and corresponding real-time beam adaptation using a dynamic multileaf collimator (DMLC). METHODS AND MATERIALS: In a multi-institutional academic and industrial collaboration, a research version of the Calypso position monitoring system was integrated with a DMLC-based four-dimensional intensity-modulated radiotherapy delivery system using a Varian 120-leaf multileaf collimator (MLC). Two important determinants of system performance-latency (i.e., elapsed time between target motion and MLC response) and geometric accuracy-were investigated. Latency was quantified by acquiring continuous megavoltage X-ray images of a moving phantom (with embedded transponders) that was tracked in real time by a circular MLC field. The latency value was input into a motion prediction algorithm within the DMLC tracking system. Geometric accuracy was calculated as the root-mean-square positional error between the target and the centroid of the MLC aperture for patient-derived three-dimensional motion trajectories comprising two lung tumor traces and one prostate trace. RESULTS: System latency was determined to be approximately 220 milliseconds. Tracking accuracy was observed to be sub-2 mm for the respiratory motion traces and sub-1 mm for prostate motion. CONCLUSION: We have developed and characterized a research version of a novel four-dimensional delivery system that integrates nonionizing radiation-based internal position monitoring and accurate real-time DMLC-based beam adaptation. This system represents a significant step toward achieving the eventual goal of geometrically ideal dose delivery to moving tumors.

Development and preliminary evaluation of a prototype audiovisual biofeedback device incorporating a patient-specific guiding waveform.

The aim of this research was to investigate the effectiveness of a novel audio-visual biofeedback respiratory training tool to reduce respiratory irregularity. The audiovisual biofeedback system acquires sample respiratory waveforms of a particular patient and computes a patient-specific waveform to guide the patient's subsequent breathing. Two visual feedback models with different displays and cognitive loads were investigated: a bar model and a wave model. The audio instructions were ascending/descending musical tones played at inhale and exhale respectively to assist in maintaining the breathing period. Free-breathing, bar model and wave model training was performed on ten volunteers for 5 min for three repeat sessions. A total of 90 respiratory waveforms were acquired. It was found that the bar model was superior to free breathing with overall rms displacement variations of 0.10 and 0.16 cm, respectively, and rms period variations of 0.77 and 0.33 s, respectively. The wave model was superior to the bar model and free breathing for all volunteers, with an overall rms displacement of 0.08 cm and rms periods of 0.2 s. The reduction in the displacement and period variations for the bar model compared with free breathing was statistically significant (p = 0.005 and 0.002, respectively); the wave model was significantly better than the bar model (p = 0.006 and 0.005, respectively). Audiovisual biofeedback with a patient-specific guiding waveform significantly reduces variations in breathing. The wave model approach reduces cycle-to-cycle variations in displacement by greater than 50% and variations in period by over 70% compared with free breathing. The planned application of this device is anatomic and functional imaging procedures and radiation therapy delivery.

Effect of n-3 fatty acid supplementation on blood glucose, lipid profile and cytokines in humans: A pilot study.

This study was undertaken to evaluate the effects of n-3 fatty acid supplementation on blood glucose, lipid profile and cytokines in humans. Twenty adult healthy subjects were supplemented with 1g/day fish oil concentrate capsules for 2 weeks. Fasting blood samples were taken at baseline and again after 2 week intervention. Fish oil supplementation significantly lowered fasting serum concentrations of total cholesterol, triacylglycerol, very low density lipoprotein and low density lipoprotein (P < 0.01). Also high density lipoprotein increased significantly compared with baseline value (P < 0.01). Fish oil did not significantly altere the fasting blood glucose concentration but significantly reduced the serum cytokines (P < 0.001). This study demonstrated that eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) supplementation altered serum lipids, lipoprotein and cytokine concentrations in normal human subjects even at the small dose of 660 mg of EPA plus DHA per day. It appears that EPA plus DHA can be a safe and perhaps beneficial supplement to inflammatory diseases.

Omega-3 fatty acid regulates inflammatory cytokine/mediator messenger RNA expression in Porphyromonas gingivalis-induced experimental periodontal disease.

INTRODUCTION: Porphyromonas gingivalis is strongly implicated in the etiology of adult periodontitis by inducing inflammatory cytokines, resulting in gingival and periodontal tissue inflammation and alveolar bone resorption. This study tested the hypothesis that supplementing the diet with omega-3 fatty acid (omega-3 FA; i.e. fish oil) would exert anti-inflammatory effects in the gingival tissues of P. gingivalis-infected rats. METHODS: Rats were fed either fish oil or corn oil diets ad libitum for 22 weeks and infected with P. gingivalis strain 381 or strain A7A1-28. After sacrifice, rat gingival tissues were excised and the RNA was isolated and analyzed for proinflammatory mediators [interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6], T helper type 1 and type 2 cytokines [interferon-gamma (IFN-gamma), IL-4, IL-10), antioxidant enzymes [catalase (CAT), superoxide dismutase (SOD)], and genes critical for eicosanoid mediator production [cyclo-oxygenase-2 (COX-2), 5-lipoxygenase (5-LO)] by reverse transcription-polymerase chain reaction using rat-specific primers. RESULTS: Rats on the omega-3 FA diet exhibited decreased proinflammatory cytokine gene expression (IL-1beta, TNF-alpha) and enhanced IFN-gamma, CAT and SOD messenger RNA expression compared to rats fed a corn oil diet, supporting a diet-induced modulation of host inflammatory reactions. Analyses of alveolar bone resorption in the rats related to gene expression profiles demonstrated significant positive correlations with IL-1beta, IL-6 and COX-2 and negative correlations with CAT and SOD. CONCLUSION: These findings suggest that diets enriched for omega-3 FA modulate the local gingival inflammatory milieu of the host following oral P. gingivalis infection, which impacts on alveolar bone resorption in rats.

Omega-3 fatty acid effect on alveolar bone loss in rats.

Gingival inflammation and alveolar bone resorption are hallmarks of adult periodontitis, elicited in response to oral micro-organisms such as Porphyromonas gingivalis. We hypothesized that omega (omega)-3 fatty acids (FA) dietary supplementation would modulate inflammatory reactions leading to periodontal disease in infected rats. Rats were fed fish oil (omega-3 FA) or corn oil (n-6 FA) diets for 22 weeks and were infected with P. gingivalis. Rats on the omega-3 FA diet exhibited elevated serum levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), documenting diet-induced changes. PCR analyses demonstrated that rats were orally colonized by P. gingivalis; increased IgG antibody levels substantiated this infection. P. gingivalis-infected rats treated with omega-3 FA had significantly less alveolar bone resorption. These results demonstrated the effectiveness of an omega-3 FA-supplemented diet in modulating alveolar bone resorption following P. gingivalis infection, and supported that omega-3 FA may be a useful adjunct in the treatment of periodontal disease.

Clinical description of an adult male with psychosis who showed FMR1 gene methylation mosaicism.

Unstable trinucleotide repeat DNA contained in numerous genes has been proposed as the underlying mechanism in the clinical phenomenon of genetic anticipation in fragile X syndrome and other neurodegenerative diseases. No clear evidence has been found for the role of these abnormal trinucleotide repeat expansion-containing genes in schizophrenia or other psychiatric disorders. This report describes an adult male with psychosis who was later found to have methylation mosaicism of the FMR1 gene. We discuss history, examination, and investigation which led to the diagnosis and treatment response of this patient.

Effect of anti-tuberculosis drugs on the iron-sequestration mechanisms of mycobacteria.

The effect of sub-lethal concentrations of isoniazid, ethambutol, rifampicin and pyrazinamide on the growth in vitro and the production of both exochelins and mycobactins by the high virulent and the South Indian low virulent strains of M. tuberculosis was examined under iron-deficient and iron-rich conditions. There was a marked decrease in the growth of both strains in the presence of increasing concentrations of all four drugs, the inhibition being total in the presence of minimal inhibitory concentrations of the drugs. It was also observed that the growth-inhibitory effect of all four drugs was slightly reversed in the presence of high concentration of iron in the medium. A significant increase was observed in the concentrations of both siderophores in the presence of all four drugs, under both iron-deficient (or) iron-rich conditions.

Isolation and characterization of siderophores and envelope proteins from mycobacteria.

Mycobacteria produce two types of siderophores, the exochelins and the mycobactins under iron-starved conditions. Attempts were initiated to separate the exochelins and mycobactins isolated from four strains of mycobacteria grown under iron-deficient conditions by chromatographic procedures. The expression of iron-regulated envelope proteins were also studied. Autoradiography of exochelins labelled with 55Fe indicates that three M. tuberculosis strains produce similar kinds of exochelins but they are different from the exochelins produced by M. Smegmatis. The mycobactins from the three M.tuberculosis strains are identical but they are different from the mycobactins produced by M. Smegmatis. SDS-PAGE electrophoresis of membrane and cell-wall fractions from four strains of mycobacteria revealed a number of proteins under iron-deficient conditions.

Effect of iron on the growth and siderophore production of mycobacteria.

To gain a better understanding of the role of iron in the pathogenesis of tuberculosis, the growth and production of siderophores were studied in the presence of different concentrations of free iron in vitro with M. smegmatis and virulent, avirulent and low virulent strains of M. tuberculosis. Increase in the concentrations of iron caused an appreciable increase in the growth (as assessed by cell dry-weight and log viable counts) of all 4 strains. This was, however accompanied by a significant decrease in the production of both exochelins and mycobactins, suggesting that these siderophores are necessary only under iron-deficient conditions. The growth and production of siderophores were significantly higher with the virulent strain of M.tuberculosis than with the avirulent (or) the low virulent strains.

Effect of hemoglobin on the growth of mycobacteria and the production of siderophores.

Hemoglobin is known to support the growth of several bacterial species. The growth and the production of siderophores by 4 strains of mycobacteria in the presence of hemoglobin was studied in vitro. The findings were compared with those obtained in the presence of equivalent concentrations of iron in the medium. Increase in the concentrations of hemoglobin caused an appreciable increase in the growth of all 4 strains. This was however, accompanied by a significant decrease in the production of both exochelins and mycobactins. It was also observed that hemoglobin supported the growth of all strains as well as that with free iron and the concentrations of both siderophores was significantly higher in the presence of hemoglobin than in that of free iron.

Three new small nucleolar RNAs that are psoralen cross-linked in vivo to unique regions of pre-rRNA.

We have recently described three novel human small nucleolar RNA species with unique nucleotide sequences, which were named E1, E2, and E3. The present article describes specific psoralen photocross-linking in whole HeLa cells of E1, E2, and E3 RNAs to nucleolar pre-rRNA. These small RNAs were cross-linked to different sections of pre-rRNA. E1 RNA was cross-linked to two segments of nucleolar pre-rRNA; one was within residues 697 to 1163 of the 5' external transcribed spacer, and the other one was between nucleotides 664 and 1021 of the 18S rRNA sequence. E2 RNA was cross-linked to a region within residues 3282 to 3667 of the 28S rRNA sequence. E3 RNA was cross-linked to a sequence between positions 1021 and 1639 of the 18S rRNA sequence. Primer extension analysis located psoralen adducts in E1, E2, and E3 RNAs that were enriched in high-molecular-weight fractions of nucleolar RNA. Some of these psoralen adducts might be cross-links of E1, E2, and E3 RNAs to large nucleolar RNA. Antisense oligodeoxynucleotide-targeted RNase H digestion of nucleolar extracts revealed accessible segments in these three small RNAs. The accessible regions were within nucleotide positions 106 to 130 of E1 RNA, positions 24 to 48 and 42 to 66 of E2 RNA, and positions 7 to 16 and about 116 to 122 of E3 RNA. Some of the molecules of these small nucleolar RNAs sedimented as if associated with larger structures when both nondenatured RNA and a nucleolar extract were analyzed.

Three small nucleolar RNAs of unique nucleotide sequences.

Three small RNA species were detected in human cells, and their cDNAs were synthesized and cloned. These RNAs are nucleolar, are 207, 154, and 135 nucleotides long, and are named E1, E2, and E3, respectively, and their unique nucleotide sequences suggest that they may belong to an additional family of small nucleolar RNAs. The 5' ends of these three RNAs do not appear to have a trimethylguanosine cap or another type of cap. Apparent homologs of these three RNAs were detected in mouse, rabbit, and frog cells, suggesting their universal importance. They are housekeeping RNA species, since they are present in all rabbit tissues analyzed.