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The New England Journal of Medicine May 2004The optimal upper limit of the normal range for prostate-specific antigen (PSA) is unknown. We investigated the prevalence of prostate cancer among men in the Prostate... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
The optimal upper limit of the normal range for prostate-specific antigen (PSA) is unknown. We investigated the prevalence of prostate cancer among men in the Prostate Cancer Prevention Trial who had a PSA level of 4.0 ng per milliliter or less.
METHODS
Of 18,882 men enrolled in the prevention trial, 9459 were randomly assigned to receive placebo and had an annual measurement of PSA and a digital rectal examination. Among these 9459 men, 2950 men never had a PSA level of more than 4.0 ng per milliliter or an abnormal digital rectal examination, had a final PSA determination, and underwent a prostate biopsy after being in the study for seven years.
RESULTS
Among the 2950 men (age range, 62 to 91 years), prostate cancer was diagnosed in 449 (15.2 percent); 67 of these 449 cancers (14.9 percent) had a Gleason score of 7 or higher. The prevalence of prostate cancer was 6.6 percent among men with a PSA level of up to 0.5 ng per milliliter, 10.1 percent among those with values of 0.6 to 1.0 ng per milliliter, 17.0 percent among those with values of 1.1 to 2.0 ng per milliliter, 23.9 percent among those with values of 2.1 to 3.0 ng per milliliter, and 26.9 percent among those with values of 3.1 to 4.0 ng per milliliter. The prevalence of high-grade cancers increased from 12.5 percent of cancers associated with a PSA level of 0.5 ng per milliliter or less to 25.0 percent of cancers associated with a PSA level of 3.1 to 4.0 ng per milliliter.
CONCLUSIONS
Biopsy-detected prostate cancer, including high-grade cancers, is not rare among men with PSA levels of 4.0 ng per milliliter or less--levels generally thought to be in the normal range.
Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Biopsy; Finasteride; Humans; Male; Middle Aged; Prevalence; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Risk
PubMed: 15163773
DOI: 10.1056/NEJMoa031918 -
Biotechnology and Bioengineering Jun 2010A novel milliliter-scale stirred tank bioreactor was developed for the cultivation of mycelium forming microorganisms on a 10 milliliter-scale. A newly designed...
A novel milliliter-scale stirred tank bioreactor was developed for the cultivation of mycelium forming microorganisms on a 10 milliliter-scale. A newly designed one-sided paddle impeller is driven magnetically and rotates freely on an axis in an unbaffled reaction vessel made of polystyrene. A rotating lamella is formed which spreads out along the reactor wall. Thus an enhanced surface-to-volume ratio of the liquid phase is generated where oxygen is introduced via surface aeration. Volumetric oxygen transfer coefficients (k(L)a) > 0.15 s(-1) were measured. The fast moving liquid lamella efficiently prevents wall growth and foaming. Mean power consumption and maximum local energy dissipation were measured as function of operating conditions in the milliliter-scale stirred tank bioreactor (V = 10 mL) and compared to a standard laboratory-scale stirred tank bioreactor with six-bladed Rushton turbines (V = 2,000 mL). Mean power consumption increases with increasing impeller speed and shows the same characteristics and values on both scales. The maximum local energy dissipation of the milliliter-scale stirred tank bioreactor was reduced compared to the laboratory-scale at the same mean volumetric power input. Hence the milliliter impeller distributes power more uniformly in the reaction medium. Based on these data a reliable and robust scale-up of fermentation processes is possible. This was demonstrated with the cultivation of the actinomycete Streptomyces tendae on both scales. It was shown that the process performances were equivalent with regard to biomass concentration, mannitol consumption and production of the pharmaceutical relevant fungicide nikkomycin Z up to a process time of 120 h. A high parallel reproducibility was observed on the milliliter-scale (standard deviation < 8%) with up to 48 stirred tank bioreactors operated in a magnetic inductive drive. Rheological behavior of the culture broth was measured and showed a highly viscous shear-thinning non-Newtonian behavior. The newly developed one-sided paddle impellers operated in unbaffled reactors on a 10 milliliter-scale with a magnetic inductive drive for up to 48 parallel bioreactors allows for the first time the parallel bioprocess development with mycelium forming microorganisms. This is especially important since these kinds of cultivations normally exhibit process times of 100 h and more. Thus the operation of parallel stirred tank reactors will have the potential to reduce process development times drastically.
Topics: Aminoglycosides; Biomass; Bioreactors; Biotechnology; Mannitol; Mycelium; Reproducibility of Results; Streptomyces
PubMed: 20198653
DOI: 10.1002/bit.22706 -
Scientific Reports Jun 2021CD4 T cell phenotyping-based blood assays have the potential to meet WHO target product profiles (TPP) of non-sputum-biomarker-based tests to diagnose tuberculosis (TB)....
CD4 T cell phenotyping-based blood assays have the potential to meet WHO target product profiles (TPP) of non-sputum-biomarker-based tests to diagnose tuberculosis (TB). Yet, substantial refinements are required to allow their implementation in clinical settings. This study assessed the real time performance of a simplified T cell activation marker (TAM)-TB assay to detect TB in adults from one millilitre of blood with a 24 h turnaround time. We recruited 479 GeneXpert positive cases and 108 symptomatic but GeneXpert negative controls from presumptive adult TB patients in the Temeke District of Dar-es-Salaam, Tanzania. TAM-TB assay accuracy was assessed by comparison with a composite reference standard comprising GeneXpert and solid culture. A single millilitre of fresh blood was processed to measure expression of CD38 or CD27 by CD4 T cells producing IFN-γ and/or TNF-α in response to a synthetic peptide pool covering the sequences of Mycobacterium tuberculosis (Mtb) ESAT-6, CFP-10 and TB10.4 antigens on a 4-color FACSCalibur apparatus. Significantly superior to CD27 in accurately diagnosing TB, the CD38-based TAM-TB assay specificity reached 93.4% for a sensitivity of 82.2% with an area under the receiver operating characteristics curve of 0.87 (95% CI 0.84-0.91). The assay performance was not significantly affected by HIV status. To conclude, we successfully implemented TAM-TB immunoassay routine testing with a 24 h turnaround time at district level in a resource limited setting. Starting from one millilitre of fresh blood and being not influenced by HIV status, TAM-TB assay format and performance appears closely compatible with the optimal TPP accuracy criteria defined by WHO for a non-sputum confirmatory TB test.
Topics: ADP-ribosyl Cyclase 1; Adolescent; Adult; Area Under Curve; CD4-Positive T-Lymphocytes; Case-Control Studies; Cigarette Smoking; Computer Systems; Female; HIV Infections; Humans; Interferon-gamma; Lymphocyte Activation; Male; Membrane Glycoproteins; Middle Aged; Mycobacterium tuberculosis; ROC Curve; Sensitivity and Specificity; Translational Research, Biomedical; Tuberculosis; Tumor Necrosis Factor-alpha; Young Adult
PubMed: 34162973
DOI: 10.1038/s41598-021-92596-z -
Phytotherapy Research : PTR Jun 2018Globalization, the modern lifestyle, immuno-suppressive agents, invasive surgical procedures, the loss of efficacies of existing drugs, and multidrug resistance are some... (Review)
Review
Globalization, the modern lifestyle, immuno-suppressive agents, invasive surgical procedures, the loss of efficacies of existing drugs, and multidrug resistance are some of the factors used to explain the rise in fungal infections in recent years. Significant advances have been made in attempts to replace existing antifungal schedules, especially with synthetic targets. The identification of other platforms for drug discovery is now entrenched in research programs across the globe. Plants offer significant benefits owing to their numerical superiority, exceedingly broad chemical basis and appealing sustainability characteristics. Furthermore, plants have a long and rich historical association with traditional approaches towards fungal diseases. These have in numerous instances served as markers in the bioassay-guided identification of the active constituents. Although the plant family Amaryllidaceae is conventionally associated with cancer and motor-neuron disease chemotherapies, around 30 of its species have been examined for antifungal activities with microgram per millilitre inhibitory activities detected in several instances. This review focuses on the nearly 40 constituents from the family, mainly isoquinoline alkaloids, which have been screened against around 50 fungal pathogens. Encouragingly, microgram per millilitre growth inhibitory activities were applicable for several of the compounds with a minimum inhibitory concentration of 4 μg/ml seen to be the lowest.
Topics: Amaryllidaceae; Antifungal Agents; Humans; Plant Extracts
PubMed: 29484733
DOI: 10.1002/ptr.6049 -
Saudi Pharmaceutical Journal : SPJ :... Nov 2020Atorvastatin (ATO) is of the statin class and is used as an orally administered lipid-lowering drug. ATO is a reversible synthetic competitive inhibitor of... (Review)
Review
Atorvastatin (ATO) is of the statin class and is used as an orally administered lipid-lowering drug. ATO is a reversible synthetic competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase thus leading to a reduction in cholesterol synthesis. It has recently been demonstrated that ATO has different pharmacological actions, which are unrelated to its lipid-lowering effects and has the ability to treat chronic airway diseases. This paper reviews the potential of ATO as an anti-inflammatory, antioxidant, and anti-proliferative agent after oral or inhaled administration. This paper discusses the advantages and disadvantages of using ATO under conditions associated with those found in the airways. This treatment could potentially be used to support the formulating of ATO as an inhaler for the treatment of chronic respiratory diseases.
PubMed: 33250642
DOI: 10.1016/j.jsps.2020.08.025 -
Saudi Journal of Biological Sciences Jan 2021Microbial surfactants are amphipathic molecules that consist of hydrophilic and hydrophobic domains, which allow partition of two fluid phases of varying degree of... (Review)
Review
Microbial surfactants are amphipathic molecules that consist of hydrophilic and hydrophobic domains, which allow partition of two fluid phases of varying degree of polarity. They are classified into two main groups: bioemulsifier and biosurfactant, depending on their molecular weight. Microbial surfactants occur in various categories according to their chemical nature and producing organisms. These biomolecules are produced by diverse groups of microorganisms including fungi, bacteria, and yeasts. Their production is significantly influenced by substrate type, fermentation technology and microbial strains. Owing to inherent multifunctional properties and assorted synthetic aptitude of the microbes, microbial surfactants are mostly preferred than their chemical counterparts for various industrial and biomedical applications including bioremediation, oil recovery; as supplements in laundry formulations and as emulsion-stabilizers in food and cosmetic industries as well as therapeutic agents in medicine. The present review discusses on production of microbial surfactants as promising and alternative broad-functional biomolecules for various biotechnological applications.
PubMed: 33424354
DOI: 10.1016/j.sjbs.2020.10.058 -
Journal of Clinical Microbiology Dec 2011Using data from 23,313 patients, we assessed whether two blood culture sets of three bottles per set would detect more pathogens than two sets of two bottles per set and...
Using data from 23,313 patients, we assessed whether two blood culture sets of three bottles per set would detect more pathogens than two sets of two bottles per set and achieve similar sensitivity to collecting three sets of two bottles per set. We also compared the yield of aerobic and anaerobic bottles. Thirty milliliters of blood was distributed to one anaerobic and two aerobic bottles. Among 26,855 collections of ≥ 60 ml within 30 min, 1,379 (5.1%) were positive for a pathogen not requiring detection in more than one set to be considered a pathogen, with 72 additional distinct pathogens detected using two 30-ml compared to two 20-ml sets of one aerobic and one anaerobic bottle (increased yield, 7.9%; 95% confidence interval [CI], 6.2 to 9.8%). For conditional pathogens requiring detection in at least two positive blood cultures for classification as pathogens (i.e., otherwise classified as contaminants), there were 162 positive detections with two 30-ml sets, of which 16 would not have been detected by two 20-ml sets (increased yield, 11.0% [95% CI, 6.4 to 17.2%]). Among 134 subjects who had three sets of 30 ml each within a 30-min interval, there was complete concordance between 60 ml of blood drawn in the first two sets of 30 ml and three 20-ml sets (P = 1.0). One aerobic bottle plus one anaerobic bottle yielded more pathogens than two aerobic bottles for organisms requiring a single (P < 0.001) and two (P = 0.04) positive sets to be defined as pathogens. In conclusion, we showed that collection of two aerobic and one anaerobic blood culture bottles per set results in improved yield compared to two bottles per set. We also confirmed that an anaerobic bottle should be included in blood culture sets.
Topics: Adolescent; Adult; Aerobiosis; Aged; Aged, 80 and over; Anaerobiosis; Blood; Female; Humans; Male; Microbiological Techniques; Middle Aged; Sensitivity and Specificity; Sepsis; Specimen Handling; Young Adult
PubMed: 21976759
DOI: 10.1128/JCM.01314-11 -
Bulletin of the National Research Centre 2022COVID-19 outbreak has engulfed different parts of the world, affecting more than 163 million people and causing more than 3 million deaths worldwide due to human... (Review)
Review
BACKGROUND
COVID-19 outbreak has engulfed different parts of the world, affecting more than 163 million people and causing more than 3 million deaths worldwide due to human transmission. Thus, it has become critical to identify the risk factors and laboratory parameters to identify patients who have high chances of worsening clinical symptoms or poor clinical outcomes. Therefore, the study aims to identify inflammatory markers that can help identify patients at increased risk for progression to critical illness, thus decreasing the risk of any mortality. Our study focussed on the predictive utility of C-reactive protein, Interleukin-6, D-dimer and Procalcitonin in assisting the management of COVID-19 patients with adverse clinical effects. Through literature search in electronic databases, we included the retrospective studies that evaluated the biomarkers among confirmed COVID-19 patients before initiation of treatment and who had a definite outcome (dead or discharged). Biomarkers were expressed in standardized difference in mean value, calculated based on study sizes and mean values between survivors and non-survivors considered the effect size. We carried out a meta-regression analysis to identify the causes of the heterogeneity between the studies.
RESULTS
Number of studies eligible for C-reactive protein, D-dimer and Interleukin-6 markers were eight, seven and four, respectively. Using random effect model revealed that the overall effect size with 95% confidence interval (CI) for C-reactive protein, D-dimer and Interleukin-6 were 1.45 (0.79-2.12) milligrams/litre, 1.12 (0.64-1.59) micrograms/millilitre Fibrinogen Equivalent Units and 1.34 (0.43-2.24) picograms/millilitre respectively was statistically significant ( < 0.05) inferring that the mean scores of these marker were significantly higher among the non-survivors compared to the survivors. Two studies were eligible for Procalcitonin marker and there was no heterogeniety ( -statistics = 0) between these studies. Therefore, fixed-effect model revealed that the overall effect size (95% CI) for Procalcitonin was 0.75 (0.30-1.21) Nanograms/millilitre was also high among non-survivors.
CONCLUSIONS
The study found that serum levels of C-reactive protein, Interleukin-6 and D-dimer showed significant elevation in non-survivors compared to survivors. Raised inflammatory markers aid in the risk stratification of COVID-19 patients and their proper management.
PubMed: 35261542
DOI: 10.1186/s42269-022-00733-z -
Scientific American Dec 1979
Topics: Animals; Blood Coagulation Disorders; Blood Glucose; Brain; Dermatologic Surgical Procedures; Diabetes Mellitus; Diabetes Mellitus, Experimental; Dogs; Drug Implants; Heparin; Humans; Insulin; Kinetics; Procainamide
PubMed: 504981
DOI: 10.1038/scientificamerican1279-66 -
Physiotherapy Canada. Physiotherapie... 2021A systematic review was conducted to investigate the effect of respiratory physiotherapy on mortality, quality of life, functional recovery, intensive care length of...
A systematic review was conducted to investigate the effect of respiratory physiotherapy on mortality, quality of life, functional recovery, intensive care length of stay, duration of ventilation, oxygenation, secretion clearance, and pulmonary mechanics for invasively ventilated adults with pneumonia. Five databases were searched for randomized trials published between January 1995 and November 2018. Study quality was assessed using a standardized Joanna Briggs Institute critical appraisal tool, and Review Manager software was used to pool the studies. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to evaluate the level of certainty of the evidence. A total of 14 studies of moderate quality included 251 subjects with pneumonia. Eight studies were pooled for meta-analysis. Interventions that increased inspiratory volume appeared to benefit secretion clearance by nearly 2 grams (mean difference [MD] 1.97; 95% CI: 0.80, 3.14; very low GRADE evidence) and increase static lung compliance immediately after treatment by more than 5 millilitres/centimetre H0 (MD 5.40 mL/cm HO; 95% CI: 2.37, 8.43; very low GRADE evidence) or by more than 6 millilitres/centimetre HO after a 20- to 30-minute delay (MD 6.86 mL/cm HO; 95% CI: 2.86, 10.86; very low GRADE evidence). No adverse events were found. Respiratory physiotherapy that increases tidal volume may benefit secretion clearance and lung compliance in invasively ventilated adults with pneumonia, but its impact on other outcomes, including mortality, length of stay, and other patient-centred outcomes, is unclear, and further research is required.
PubMed: 35106019
DOI: 10.3138/ptc-2019-0025