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Biomedical subjects

J Anderson

Publications and source records attributed to J Anderson.

At least 217 records · Page 12Linked to original sources

The value of prostate specific antigen (PSA) density and free: total PSA ratio in selecting patients with a normal digital rectal examination and intermediate total PSA levels for further investigation.

OBJECTIVES: To examine the use of prostate-specific antigen (PSA) density (PSAD) and free to total PSA ratio (f/tPSA) in enhancing the specificity of PSA in the diagnosis of prostate cancer in patients with a total PSA (tPSA) of 4-10 ng/mL and with a normal digital rectal examination (DRE). PATIENTS AND METHODS: The study comprised 77 consecutive men in whom the fPSA and tPSA levels were obtained before DRE and transrectal ultrasonography-guided sextant prostate biopsy. Prostate cancer was found in 39 patients and the histology was benign in 38. Receiver operator characteristic curves, obtained from all 77 patients, were used to determine the optimal thresholds for PSAD and f/tPSA in detecting cancer. A subset of 28 patients, including seven with prostate cancer, was identified who had a normal DRE and a tPSA of 4-10 ng/mL; PSAD and f/tPSA values were applied at the optimal thresholds to assess their use in identifying those patients with cancer. RESULTS: When applied to the selected group of 28 patients, the PSAD (threshold 0.15) failed to identify any with prostate cancer. The f/tPSA (threshold 0.12) yielded a sensitivity of 65% and a specificity of 38%, identifying only three of seven patients with cancer. By increasing the threshold to 0.25, six patients were correctly identified, giving a sensitivity of 86%, with a lower specificity of 14%. CONCLUSIONS: These findings suggest that the neither PSAD nor f/tPSA either significantly reduce the negative biopsy rate or identify patients at greater risk of prostate cancer, particularly when the tPSA is equivocal at 4-10 ng/mL.

Aged↗

A randomized trial of three iron dextran infusion methods for anemia in EPO-treated dialysis patients.

Forty-three hemodialysis patients receiving recombinant erythropoietin (rHuEPO, epoietin alpha) were randomized to receive intravenous iron dextran as a total-dose infusion, 500-mg infusion to total dose, or 100-mg bolus to total dose, in each case during the dialysis procedure. The dose of iron dextran was calculated from the patient's existing hemoglobin to achieve a desired hemoglobin. Patients were eligible to receive intravenous iron dextran if they had a serum ferritin of < or = 100 ng/mL or a serum ferritin of 100 to 200 ng/mL, along with a transferrin saturation of < or = 19%. Patients were excluded if they had prior therapy with iron dextran, aluminum intoxication, or transfusion during the study. The time to the maximum hemoglobin, acute adverse reactions, and delayed adverse reactions were analyzed statistically, and no differences were seen in any of the three groups. Total-dose intravenous iron dextran infusion is safe, convenient, less expensive, and as efficacious as divided-dose infusions.

Anemia↗

The transthoracic impedance cardiogram is a potential haemodynamic sensor for an automated external defibrillator.

AIMS: The American Heart Association has endorsed the concept of Public Access Defibrillation. However, there have been reports of inappropriate direct current shocks from automatic external defibrillators. The specificity of automatic external defibrillators for shockable rhythms may be improved by the incorporation of a haemodynamic sensor. METHODS AND RESULTS: This study examined the use of four parameters extracted from the impedance cardiogram i.e. Peak dz/dt (the peak of the impedance cardiogram measured from the line dz/dt=0 ohms(-1)), Peak-trough (the peak-to-trough measurement of the impedance cardiogram ohms(-1)), Area 1 (the area under the C wave of the impedance cardiogram above the line dz/dt=0 mohm) and Area 2 (the area under the impedance cardiogram 50 ms on either side of the Peak and above the line dz/dt=0 mohm) as predictors of cardiac output. At 116 cardiac arrest calls the ECG and impedance cardiogram were recorded through two ECG/defibrillator pads placed in an antero-apical position. Nine recordings were rejected for artefact. The rhythm recorded in the remaining 107 calls was asystole (19), ventricular fibrillation (14), agonal rhythm (20), electromechanical dissociation (22), ventricular tachycardia (27) and sinus rhythm (5). These rhythms were divided into those associated with haemodynamic collapse i.e. no pulse -- asystole, ventricular fibrillation, agonal rhythm, electromechanical dissociation and shockable ventricular tachycardia (associated with loss of consciousness, pulselessness or a systolic blood pressure of <80 mmHg) (Group 1) and those associated with a satisfactory cardiac output i.e. non-shockable ventricular tachycardia (conscious with a pulse) and sinus rhythm (Group 2). On univariate analysis each of the four impedance cardiogram parameters were significantly greater in Group 2 than Group 1 (P<0.001). On multivariate analysis the parameters which best differentiated the two groups were Area 1 and Peak-trough. CONCLUSION: Thus the impedance cardiogram is a potential haemodynamic sensor for an automatic external defibrillator.

Adult↗

Radon-222 and gamma ray levels associated with the collection, processing, transmission, and utilization of natural gas.

The natural gas industry in British Columbia was investigated for exposure to radioactive contaminants such as radon-222 and lead-210. Radon activity associated with the gathering system ranged from 7-921 Bq/m3. The pipelines to the processing facility contained sludge that had a mean lead-210 activity of 0.494 Bq/g (0.379 standard deviation [SD]) and a mean radium-226 activity of 0.417 (0.398 SD). Within the processing facility the highest levels of radon were associated with propane production streams, and activities as high as 4958 Bq/m3 were found. Equipment handling these streams was also found to have a buildup of scale with lead-210, radium-224, and radium-226 activity. The transmission of salable gas to the consumer indicated a decrease in radon activity that was slightly lower than the estimated radon activity based on the half-life of radon, the distance from the production facility, and the speed of gas transmission. The risk of radon exposure to the worker was deemed well below the guidelines and would be controlled more than adequately by means of the occupational standards for the natural gas components. Gamma ray exposure was also well below the occupational standards. Radon exposure to the consumer was virtually nonexistent in the Vancouver region from both natural gas and propane. Although this might not be the case for consumers of propane closer to the production facilities, its contribution is likely to be minimal.

British Columbia↗

Industrial hygiene aspects of a sampling survey at a bleached-kraft pulp mill in British Columbia.

To validate exposure estimates used to investigate correlations between exposure and cancer risk, 1678 personal measurements were collected for 46 job titles during 73 day shifts at a bleached-kraft pulp mill. Measurements included shift-long average and short-term exposures to carbon monoxide, chlorine dioxide (ClO2), and hydrogen sulfide; and shift-long average exposures to calcium oxide and wood dust (WD). Overall results indicate low levels of exposure with a few noteworthy exceptions. Although ClO2 was the exclusive bleaching agent, 77 area samples indicated that chlorine (Cl2), not ClO2 was present in all areas apart from the chemical preparation area (chem-prep) and during a pulp spill. The highest shift-long exposures to Cl2 were measured in the chip yard and are attributed to uncontrolled stack emissions. Finally, WD samples collected from several laborers significantly exceeded regulatory limits, with the highest exposures measured in the steam and recovery area. For short-term exposures to ClO2 in chem-prep, 12 of 17 data-logging electro-chemical sensor sample results showed at least one peak that exceeded the short-term exposure limit of 0.3 ppm. The use of data-logging equipment quantified short-term exposures that previously had been characterized only anecdotally. The peaks were correlated with tasks and upset conditions and, given their transient nature, these exceedances could not have been detected using shift-long average-based sampling devices. Since the respiratory effects of significant short-term exposures to irritant gases such as Cl2 and ClO2 are well-documented, data-logging instruments are necessary to characterize exposures in the pulp and paper industry.

Air Pollutants, Occupational↗

Simplified surveillance for nosocomial bloodstream infections.

OBJECTIVE: To compare a surveillance definition of noso comial bloodstream infections requiring only microbiology data to the Centers for Disease Control and Prevention's (CDC) current definition. SETTING: Six teaching hospitals. METHODS: We classified a representative sample of 73 positive blood cultures from six hospitals growing common skin contaminant isolates using a definition for bacteremia requiring only microbiology data and the CDC definition for primary bloodstream infection (National Nosocomial Infections Surveillance [NNIS] System review method). The classifications assigned during routine prospective surveillance also were noted, and the time required to classify isolates by the two methods was compared. RESULTS: Among 65 blood cultures growing common skin contaminant isolates obtained from adults, the agreement rate between the microbiology data method and the NNIS review method was 91%. Agreement was significantly poorer for the eight blood cultures growing common skin contaminant isolates obtained from pediatric patients. The microbiology data method requires approximately 20 minutes less time per isolate than does routine surveillance. CONCLUSIONS: A definition based on microbiology data alone yields the same result as the CDC's definition in the large majority of instances. It is more resource-efficient than the CDC's current definition.

Adult↗

Apert syndrome mutations in fibroblast growth factor receptor 2 exhibit increased affinity for FGF ligand.

Dominantly acting mutations of the fibroblast growth factor (FGF) receptor 2 (FGFR2) gene have been implicated in various craniosynostosis syndromes. Apert syndrome, characterized in addition by syndactyly of the limbs, involves specific mutations at two adjacent residues, Ser252Trp and Pro253Arg, predicted to lie in the linker region between IgII and IgIII of the FGFR2 ligand-binding domain. We have analysed the interaction of FGF ligands with wild-type and Apert-type mutant FGFR2 ectodomains in solution. Wild-type and Apert-type receptors form a complex with FGF ligands with a stoichiometry of 2:2 (ligand:receptor). The kinetics and specificity of ligand binding to wild-type and Apert mutant receptors have been analysed using surface plasmon resonance techniques. This reveals that Apert mutations, compared with wild-type, exhibit a selective decrease in the dissociation kinetics of FGF2, but not of other FGF ligands examined. In contrast, the substitution Ser252Leu in FGFR2, previously observed in several asymptomatic individuals, exhibited wild-type kinetics. These findings indicate that Apert syndrome arises as a result of increased affinity of mutant receptors for specific FGF ligands which leads to activation of signalling under conditions where availability of ligand is limiting.

Acrocephalosyndactylia↗

Attitudes towards routine human immunodeficiency virus (HIV) screening and fertility treatment in HIV positive patients--a UK survey.

Of 70 fertility units licensed by the Human Fertilisation and Embryology Authority in the UK, 58 responded to a questionnaire regarding attitudes towards human immunodeficiency virus (HIV) screening and fertility treatment in HIV positive patients in November 1995. Of these 58 centres, 23 only performed routine screening for HIV for both partners, 24 for hepatitis B and eight for hepatitis C. In the event of a positive result in the male, fertility treatment would be offered in the form of donor insemination (n = 21), intrauterine insemination (IUI) after sperm washing (n = 21), and in-vitro fertilization (IVF) (n = 1). If the woman was HIV positive, two centres would offer IUI and three centres IVF. Nine centres had already provided treatment for couples in whom the male partner was HIV positive and two centres to HIV positive women.

Attitude to Health↗

The clinical features of immunoglobulin light-chain (AL) amyloidosis with heart involvement.

We reviewed clinical presentation, investigations, therapy, prognosis and outcome of 232 patients with primary (AL) cardiac amyloidosis. There were 142 men and 90 women. Median age at presentation was 59 years (range 29-85). AL heart disease was unusual both in patients under the age of 40 (3.0%) and in non-Caucasians (6.5%). Fatigue and weakness were the commonest presenting symptoms. Hallmark features of periorbital ecchymoses and macroglossia were present in 12.5% and 27.2%, respectively. AL cardiac amyloidosis was unusual in isolation (3.9%), and most frequently patients had features of multiorgan dysfunction; heavy proteinuria and features of malabsorption predominating in this respect. Heart involvement represents the worst prognostic indicator, with a median survival from diagnosis of 1.08 years, falling to 0.75 years with the onset of heart failure. Current therapeutic procedures appear to prolong survival, with left ventricular wall thickness, mass and ejection fraction on echocardiography and late potentials on signal averaged electrocardiography of use in prognostic stratification. Cardiac involvement from AL amyloidosis is rapidly fatal. It should be suspected in all patients with heart failure who have wall thickening on echo, normal chamber sizes, low EKG voltages and evidence suggesting a multisystem disease.

Adult↗

DQA-DQB linkage in Old World monkeys.

The MHC DQ region in nonhuman primates, as in humans, consists of alpha and beta chains that are polymorphic with strong linkage disequilibrium between certain DQA-DQB alleles. Not only are contemporary HLA class II allelic variants present in evolutionarily distant species, but we demonstrate that linkages between loci also bear ancient roots. In unrelated baboons (Papio cynocephalus anubis) and family segregation analysis of pigtailed macaques (Macaca nemestrina) we found cis-linkages between DQA1*01 and DQB1*05 or *06, between DQA1*05 and DQB1*03, and between DQA1*03 and DQB1*03 alleles, all of which are also prominent in modern humans. In contrast, one linkage that has not been seen in humans, between DQA1*05 and DQB1*06 alleles, was also found. These patterns of selective linkage disequilibrium imply evolutionary mechanisms following the divergence of species that constrain the diversity of haplotypes which evolve.

Alleles↗

Efficacy of MK-991 (L-743,872), a semisynthetic pneumocandin, in murine models of Pneumocystis carinii.

In addition to its potent efficacy in animal models against Candida sp., Aspergillus fumigatus, and Histoplasma capsulatum, the clinical candidate pneumocandin MK-991 (formerly L-743,872) was also extremely potent against Pneumocystis carinii in models of immune-compromised animals. MK-991 was approximately 14 times more potent than the original natural product lead, pneumocandin B0. The 90% effective dose (ED90) of MK-991 for cyst clearance in the rat model for pneumocystis was 0.011 mg/kg of body weight when delivered parenterally for 4 days twice a day (b.i.d.). In a mouse model, under the same experimental parameters, the ED90 was 0.02 mg/kg. MK-991 was also effective orally, with an ED90 for cyst clearance of 2.2 mg/kg against acute infection in rats (b.i.d. for 4 days). Complete prevention of P. carinii development was achieved in immunocompromised mice at a daily oral dose of 2.25 mg/kg. As reported previously for other pneumocandins and echinocandins, MK-991 selectively prevented the development of P. carinii cysts. When used as a prophylactic agent, neither stage of the organism appeared in the lungs of animals. In response to an acute infection, cysts were eliminated rapidly, while trophozoite forms persisted. Despite good efficacy as an oral agent in murine models, the low oral absorption of this class may limit the use of MK-991 to parenteral therapy.

Administration, Oral↗

Blood cultures positive for coagulase-negative staphylococci: antisepsis, pseudobacteremia, and therapy of patients.

A blood culture cohort study investigating issues related to isolation of coagulase-negative staphylococci (CoNS) and other skin microflora is reported. Data were collected over 12 weeks to determine the incidence of significant CoNS bacteremia versus that of pseudobacteremia (contaminants) and to evaluate drug therapy in patients with cultures positive for CoNS. In addition, the effectiveness of 0.2% chlorine peroxide as a bactericidal disinfectant was compared to that of 10% providone iodine. A total of 3,276 cultures of blood from 1,433 patients were evaluated in the study. Eighty-nine cultures were positive for skin flora, with 81 of 89 (91%) involving CoNS. The incidence of significant CoNS bacteremia was 20 of 81 (24.7%), that of indeterminate bacteremia was 10 of 81 (12.3%), and that of contamination was 59 of 81 (72.8%). The incidence of significant bacteremia involving CoNS was double the 10 to 12% rate based on previous estimations at our institutions. In tests with the two bactericidal disinfectants, 22 of 1,639 cultures (1.3%) in the chlorine peroxide group versus 37 of 1,637 (2.3%) in the providone iodine group were considered contaminated (P = 0.065). Rates of contamination for venipuncture versus catheter collection were not significantly different (P = 0.46). The overall contamination rate was 59 of 3,276 (1.8%), which is consistent with the lower end of published quality assurance benchmark standards. The low rate was believed to be due to the professional phlebotomy staff in our institutions. There was excellent agreement between retrospective analysis by reviewers, when formal criteria were used, and the attending physicians' intuitive clinical impressions in the classification of significant bloodstream infections (100% agreement) or contamination (95% agreement). However, physicians still used antimicrobial agents to treat nearly one-half of the patients with contaminated blood cultures, with vancomycin being misused in 34% of patients. In addition, 10% of patients with significant bacteremia were treated with inappropriate agents. There were no significant adverse events or prolonged hospital stays due to the unnecessary use of vancomycin; however, the additional costs of treating patients whose cultures contained CoNS contaminants was estimated to be $1,000 per patient. Measures to limit the unnecessary use of vancomycin (and other agents) are important.

Adult↗

Identification of a translation initiation factor 3 (eIF3) core complex, conserved in yeast and mammals, that interacts with eIF5.

Only five of the nine subunits of human eukaryotic translation initiation factor 3 (eIF3) have recognizable homologs encoded in the Saccharomyces cerevisiae genome, and only two of these (Prt1p and Tif34p) were identified previously as subunits of yeast eIF3. We purified a polyhistidine-tagged form of Prt1p (His-Prt1p) by Ni2+ affinity and gel filtration chromatography and obtained a complex of approximately 600 kDa composed of six polypeptides whose copurification was completely dependent on the polyhistidine tag on His-Prt1p. All five polypeptides associated with His-Prt1p were identified by mass spectrometry, and four were found to be the other putative homologs of human eIF3 subunits encoded in S. cerevisiae: YBR079c/Tif32p, Nip1p, Tif34p, and YDR429c/Tif35p. The fifth Prt1p-associated protein was eIF5, an initiation factor not previously known to interact with eIF3. The purified complex could rescue Met-tRNAiMet binding to 40S ribosomes in defective extracts from a prt1 mutant or extracts from which Nip1p had been depleted, indicating that it possesses a known biochemical activity of eIF3. These findings suggest that Tif32p, Nip1p, Prt1p, Tif34p, and Tif35p comprise an eIF3 core complex, conserved between yeast and mammals, that stably interacts with eIF5. Nip1p bound to eIF5 in yeast two-hybrid and in vitro protein binding assays. Interestingly, Sui1p also interacts with Nip1p, and both eIF5 and Sui1p have been implicated in accurate recognition of the AUG start codon. Thus, eIF5 and Sui1p may be recruited to the 40S ribosomes through physical interactions with the Nip1p subunit of eIF3.

Animals↗

Adult polyglucosan body disease associated with an extrapyramidal syndrome.

A 50 year old patient is described who presented with parkinsonism, frontal dementia, peripheral neuropathy, neurogenic bladder, and upper motor neuron signs. No improvement in objective measurements of extrapyramidal dysfunction were seen with an incremental apomorphine test or more prolonged oral dopamine challenge. Neurophysiology disclosed changes compatible with a diffuse axonal neuropathy and pathological examination of a length of sural nerve taken at biopsy showed multiple polyglucosan bodies characteristic of adult polyglucosan body disease (APGBD). This case underlines the diverse clinical presentation of this rare neurological disease and the importance of recognising the unusual association of clinical features in making the diagnosis. APGBD should be included in the differential diagnosis of parkinsonism unresponsive to dopaminergic therapy.

Adult↗

Findings of mild traumatic brain injury in combat veterans with PTSD and a history of blast concussion.

Veterans with chronic posttraumatic stress disorder were evaluated for a history of blast concussion, controlling for confounding conditions. Electroencephalograms were analyzed by discriminant function for traumatic brain injury. A difference was found in discriminant scores between veterans with and without blast concussion. More members of the blast group had attentional symptoms and attentional dysfunction. Combat veterans with a remote history of blast injury have persistent electroencephalographic features of traumatic brain injury as well as attentional problems. The authors hypothesize that these constitute a type of chronic postconcussive syndrome that has cognitive and mood symptoms overlapping those of posttraumatic stress disorder.

Adult↗