False alarms: burning issues.
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Equipment Failure↗
Biomedical subjects
C Newman
Publications and source records attributed to C Newman.
Identification of non-B human immunodeficiency virus type 1 subtypes in rural Georgia.
As part of an ongoing molecular epidemiological investigation of human immunodeficiency virus type 1 (HIV-1) in rural Georgia, the 5' half of reverse transcriptase (RT) genotypes from 30 patients was sequenced and phylogenetically analyzed. Two patients, GA132 and GA169, were infected with pol sequences of non-B subtype origin that were found to cluster phylogenetically with subtype A-E of Thai origin. Sliding window bootstrap analysis of GA169 showed clear evidence of A/B recombination within the pol gene segment, whereas in the other patient, GA132, no break point within RT could be identified. Interestingly, pairwise comparisons between these 2 patients' C2-V3 env region revealed a 13.5% divergence. However, similar comparisons within the non-B pol segments yielded a 1.23% nucleotide divergence, which suggests a complex phylogenetic and epidemiological history of the subtype A pol genotype in this region. These data demonstrate an increasing diversity of HIV-1 subtypes and the potential emergence of previously unidentified HIV-1 A-E/B recombinants in the rural United States.
Adult↗
Coccidiosis in the European badger (Meles meles) from England, an epidemiological study.
In total 445 faecal samples were collected from 259 European badgers (Meles meles) in Wytham Woods, Oxfordshire, UK (462080). Microscopical examination revealed infection with 2 species of coccidia Eimeria melis and Isospora melis. From the initial examination of each animal, point prevalence rates of 0.44 and 0.35 were calculated for Eimeria and Isospora respectively. The intensity of infection was significantly greater for Eimeria than Isopora and the distribution of intensities was highly skewed for both species, with a few individuals shedding the majority of oocysts. Incidence and recovery rates for both coccidia species were calculated from longitudinal data collected at 3-monthly intervals from a subset of the adult badger population, and the predicted prevalence rates based on these were similar to the point prevalence rates. This suggests little, if any, parasite-induced mortality in the adult population. In contrast, there was a marked and significant reduction in the point prevalence and intensity of infection with Eimeria from cub to adult badger suggesting a degree of acquired immunity to Eimeria melis on initial exposure and/or that there is significant Eimeria-associated mortality in the cub population. No such relationship was found for Isospora infection. In those adult badgers with co-infections there was a direct relationship between the intensity of Eimeria and Isospora. The taxonomic status of these parasites suggests a heteroxenous life-cycle for I. melis, and direct transmission of E. melis. However, the greater than expected prevalence of co-infection is consistent with a common source of infection, such as communal latrines.
Age Factors↗
The TRAPP complex is a nucleotide exchanger for Ypt1 and Ypt31/32.
In yeast, the Ypt1 GTPase is required for ER-to-cis-Golgi and cis-to-medial-Golgi protein transport, while Ypt31/32 are a functional pair of GTPases essential for exit from the trans-Golgi. We have previously identified a Ypt1 guanine nucleotide exchange factor (GEF) activity and characterized it as a large membrane-associated protein complex that localizes to the Golgi and can be extracted from the membrane by salt, but not by detergent. TRAPP is a large protein complex that is required for ER-to-Golgi transport and that has properties similar to those of Ypt1 GEF. Here we show that TRAPP has Ypt1 GEF activity. GST-tagged Bet3p or Bet5p, two of the TRAPP subunits, were expressed in yeast cells and were precipitated by glutathione-agarose (GA) beads. The resulting precipitates can stimulate both GDP release and GTP uptake by Ypt1p. The majority of the Ypt1 GEF activity associated with the GST-Bet3p precipitate has an apparent molecular weight of > 670 kDa, indicating that the GEF activity resides in the TRAPP complex. Surprisingly, TRAPP can also stimulate nucleotide exchange on the Ypt31/32 GTPases, but not on Sec4p, a Ypt-family GTPase required for the last step of the exocytic pathway. Like the previously characterized Ypt1 GEF, the TRAPP Ypt1-GEF activity can be inhibited by the nucleotide-free Ypt1-D124N mutant protein. This mutant protein also inhibits the Ypt32 GEF activity of TRAPP. Coprecipitation and overexpression studies suggest that TRAPP can act as a GEF for Ypt1 and Ypt31/32 in vivo. These data suggest the exciting possibility that a GEF complex common to Ypt1 and Ypt31/32 might coordinate the function of these GTPases in entry into and exit from the Golgi.
Biological Transport↗
The perceived position of the hand in space.
This paper reports a series of experiments of the perceived position of the hand in egocentric space. The experiments focused on the bias in the proprioceptively perceived position of the hand at a series of locations spanning the midline from left to right. Perceived position was tested in a matching paradigm, in which subjects indicated the perceived position of a target, which could have been either a visual stimulus or their own fingertip, by placing the index finger of the other hand in the corresponding location on the other side of a fixed surface. Both the constant error, or bias, and the variable error, or consistency of matching attempts, were measured. Experiment 1 showed that (1) there is a far-left advantage in matching tasks, such that errors in perceived position are significantly lower in extreme-left positions than in extreme-right positions, and (2) there is a strong hand-bias effect in the absence of vision, such that the perceived positions of the left and right index fingertips held in the same actual target position in fact differ significantly. Experiments 2 and 3 demonstrated that this hand-bias effect is genuinely due to errors in the perceived position of the matched hand, and not to the attempt at matching it with the other hand. These results suggest that there is no unifying representation of egocentric, proprioceptive space. Rather, separate representations appear to be maintained for each effector. The bias of these representations may reflect the motor function of that effector.
Adolescent↗
Characterization of a third CCR5 amplicon from CCR5-delta32-heterozygous HIV-1-infected individuals.
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Base Sequence↗
Phylogenetic examination of HIV type 1 glycoprotein 120-V3 sequences in patients from rural Georgia.
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Adult↗
Control of cell migration during Caenorhabditis elegans development.
In Caenorhabditis elegans, cell migration is guided by localized cues, including molecules such as EGL-17/FGF and UNC-6/netrin. These external cues are linked to an intracellular response to migrate, at least in part, by CED-5, a homolog of DOCK180/MBC, and MIG-2, a Rac-like GTPase. In addition, metalloproteases are required for a cell migration that controls organ shape.
Animals↗
On the perceived time of voluntary actions.
When do we think we move when we make a voluntary action? Previous studies have pointed to an anticipatory awareness of action (i.e. we think we move before we actually do), but have not investigated the content or locus of motor awareness. In the experiment reported here the authors localize the time of awareness of the first movement in a sequence within the context of a specific information-processing model. The results suggest that our awareness of our own actions is associated with some pre-motor event after the initial intention and preparation of action, but before the assembly and dispatch of the actual motor command to the muscles.
Adult↗
Accidental child poisoning. Child resistant packaging should be the legal requirement.
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Antitussive Agents↗
Telemedicine diagnosis of eye disorders by direct ophthalmoscopy. A pilot study.
OBJECTIVE: To report a pilot study of telemedical direct ophthalmoscopy in the diagnosis of acquired immune deficiency syndrome (AIDS)-related retinopathy in a human immunodeficiency virus (HIV)-positive population and in the diagnosis of glaucoma, cataract, and retinopathy in a diabetic population. DESIGN: Prospective comparative case series. PARTICIPANTS: Seventeen HIV-positive and 20 diabetic patients. METHODS: A direct ophthalmoscope custom-fitted with a digital microcamera capable of transmitting images from any of 61 sites within the Georgia Statewide Telemedicine Program was used by a nonophthalmologist to examine 34 eyes of 17 HIV-positive patients and 39 eyes of 20 patients with diabetes. Fundus images were transmitted in real-time to a reviewing ophthalmologist. An in-person, comprehensive examination including indirect ophthalmoscopy, was performed by a second ophthalmologist. Telemedical examination was compared to the in-person comprehensive examination. RESULTS: For the HIV study, 21 eyes did not show HIV retinopathy (noninfectious retinopathy with cotton-wool spots) by in-person examination. Telemedical examination correctly identified 20 of these eyes as disease-free (specificity = 95%). HIV retinopathy was present in 12 of the 34 eyes by in-person evaluation with telemedical examination correctly diagnosing 10 of these eyes (sensitivity = 83%). One eye with dense cataract and retinal detachment was unable to be evaluated ophthalmoscopically by either in-person or telemedical examination. Telemedical and in-person assessments for HIV retinopathy were identical in 100% of eyes without cataract. Disagreement in diagnosis between telemedical and in-person examination was associated with cataract (P < 0.0007). For the diabetes study, because of an inadequate image, telemedical examination was unable to classify 46% and 36% of eyes for glaucoma and diabetic retinopathy, respectively. Inability to make a telemedical determination for glaucoma (P < 0.011), nonproliferative (P < 0.064) and proliferative (P < 0.064) diabetic retinopathy was associated with cataract. Of the eyes that were able to be assessed by telemedical examination for diabetic retinopathy (n = 25), glaucoma (n = 21), and cataract (n = 39), the accuracy was poor (sensitivity = 29%, 50%, and 41%, respectively). Telemedical examination for diabetic retinopathy and glaucoma was more likely to agree with in-person examination in eyes without cataract as compared to eyes with cataract (not statistically significant). CONCLUSION: Telemedical direct ophthalmoscopic, real-time fundus imaging may provide a valuable means for providing ophthalmic consultation to the primary care physician in younger patients without lens or media opacity, but is inadequate for eyes with any degree of lens or media opacity.
Acquired Immunodeficiency Syndrome↗
Mortality in potential arterial switch candidates with transposition of the great arteries.
OBJECTIVES: We reviewed the factors contributing to or causing death before surgery in neonates with d-transposition of the great arteries (TGA) despite anatomy suitable for the arterial switch operation (ASO) to develop strategies to minimize preoperative attrition. BACKGROUND: Currently the ASO for neonates with TGA carries a low operative mortality. However, there is a paucity of information regarding the patients who die before the ASO. Strategies to ensure survival to operation are of importance to improve overall outcome. METHODS: We reviewed all neonates with TGA and patent forearm ovale (PFO) < or = 2 mm, a birthweight <2 kg, or who died before surgery, between 1988 and 1996. RESULTS: We identified 12 out of 295 neonates with TGA (4.1%) with anatomy suitable for the ASO who died prior to surgery. All had TGA/intact ventricular septum (IVS) and presented with a severely restrictive PFO. In 11 of 12 cases the cause of death was attributed to the sequelae of profound hypoxemia from inadequate mixing. Contributing factors were prematurity, 41.7%; severe respiratory distress syndrome, 25%; and persistent pulmonary hypertension of the newborn (PPHN), 16.7%. All patients received prostaglandin E1 (PGE1) infusion. Urgent balloon atrial sepstostomy (BAS) was performed in 66.7% with improved oxygenation. No cases were diagnosed prenatally. In contrast, all patients with a PFO < or = 2 mm who survived to ASO had a significantly better response to PGE1 infusion (p=0.03) than nonsurvivors. The ASO was accomplished without mortality in four of nine with a weight <2 kg. CONCLUSIONS: Of those neonates admitted with TGA, 4.1% died before surgery. Eleven of 12 (3.7%) died due to consequences of inadequate interatrial mixing despite PGE1 infusion. Earlier diagnosis and BAS are critically important in determining survival. Early ASO may improve survival in patients weighing <2 kg. Prenatal diagnosis with delivery in a high-risk obstetrical unit with facilities for immediate BAS and supportive therapy for pulmonary hypertension and ventricular failure may be necessary to salvage this group of patients.
Cause of Death↗
Application of random amplified polymorphic DNA PCR for genomic analysis of HIV-1-infected individuals.
Random amplified polymorphic DNA polymerase chain reaction (RAPD-PCR) is a DNA fingerprinting technique used to detect genomic polymorphisms. We employed sixteen different RAPD-PCR 10-mer primers to amplify DNA from the peripheral blood mononuclear cells (PBMC) of 80 HIV-1-infected individuals. These individuals were previously identified as either heterozygotes (+ /delta32) and homozygotes (+/+) for the CCR5 locus by PCR with gene specific primers. Four of the sixteen randomly selected RAPD primers produced distinguishable banding profiles between CCR5 (+/delta32) heterozygotes and CCR5 (+/+ ) homozygotes. Direct sequencing of some RAPD-PCR products obtained with one of the four RAPD primers that were tested yielded clearly readable, but limited sequences, which were similar to portions of the previously published sequences for (+/+ ) homozygotes (98% similarity) and (+/delta32) heterozygotes (87% similarity) of the CCR5 alleles. Thus, the RAPD-PCR technique may be useful for the identification of human molecular markers that may correlate with susceptibility to HIV-1-infection, or differences in disease progression among HIV-l-infected individuals.
Base Sequence↗
Exogenous bovine surfactant suppresses tumor necrosis factor-alpha release by murine macrophages stimulated by genital mycoplasmas.
Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that appears to play a significant role in the development of neonatal chronic lung disease (CLD). Inflammation and CLD are also associated with respiratory tract colonization with genital mycoplasmas. The possible protective roles of surfactant in mitigating the inflammatory response to these microbes were investigated. Murine RAW 264.7 macrophages were preincubated with an exogenous surfactant and exposed overnight to sterile media, lipopolysaccharide (LPS), Mycoplasma hominis, or Ureaplasma urealyticum. Macrophages released TNF-alpha in response to challenge with LPS, U. urealyticum, and M. hominis in a concentration-dependent fashion. Surfactant suppressed LPS and M. hominis induced TNF-alpha production in a dose-dependent manner but suppressed U. urealyticum-mediated TNF-alpha production only at the higher dose tested. Similar effects were seen in hyperoxia (95% O2). Thus, exogenous bovine surfactant significantly inhibits the production of TNF-alpha by murine macrophages stimulated with genital mycoplasmas and bacterial LPS.
Animals↗
Communicate: organisational issues and their relevance for clinical evaluation.
This paper reports the first findings of a two year project funded by the NHS Executive North Thames to provide an independent evaluation of Communicate, Action for Dysphasic Adults' training programme for carers of older people with communication impairments. The project comprises an organisational evaluation (January-July 1998) to review the use of Communicate by purchasers nationally and in the North Thames health region, and (from September 1998) a clinical evaluation in North Thames region, to investigate outcomes for communicatively impaired people themselves and for training participants. The paper outlines the research design and progress so far before presenting initial findings. It concludes by discussing the relevance of organisational issues and social science research insights to the forthcoming clinical evaluation.
Aphasia↗
A rapidly developing violaceous plaque.
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Aged↗
A prospective randomized trial of an antibiotic- and antiseptic-coated central venous catheter in the prevention of catheter-related infections.
OBJECTIVE: To test the efficacy of the ARROWgard (Arrow International Inc, Reading, Pa) central venous catheter (CVC) coated with silver sulfadiazine and chlorhexidine (A-CVC) in the prevention of CVC-related infections. DESIGN: Prospective, randomized trial. SETTING: A tertiary care medical center. PATIENTS AND INTERVENTION: Two hundred eighty-two patients who required CVC placement were evaluated in this study. Patients were prospectively randomized to receive either a standard CVC (S-CVC) or the A-CVC. Only fresh-stick double- and triple-lumen catheters were studied. MAIN OUTCOME MEASURES: Patients were evaluated for catheter site inflammation, catheter site colonization, local catheter-related infection, and catheter-related septicemia. RESULTS: The 2 groups were matched for age, percentage in the intensive care unit, percentage receiving total parenteral nutrition, percentage with triple-lumen catheters, and duration of catheterization. Rates of catheter site inflammation in the 2 groups were similar (12% vs 10%, S-CVC group and A-CVC group, respectively). The A-CVC was associated with a significantly decreased catheter site colonization rate (49% vs 28%; 43% reduction; P<.001) and local catheter-related infection rate (22.4% vs 5.8%; 74% reduction; P<.001). Rates of catheter-related septicemia were reduced by 41% in the A-CVC group (6.4% vs 3.8%, S-CVC group and A-CVC group, respectively), but this was not statistically significant. CONCLUSIONS: Despite a marked decrease in catheter site colonization and catheter-related infection rates, the A-CVC did not significantly reduce the incidence of catheter-related septicemia. This may be due to a greater pathogenic dependence on catheter hub contamination rather than catheter site colonization or local catheter-related infection, or the relatively short (5.2 days) duration of catheterization in this study.
Anti-Infective Agents, Local↗
Perception of preventive health needs in a prostate-cancer screening population: a preliminary report.
In follow-up of a screening program for prostate cancer, 192 men from the urban Denver area and 244 men from rural northeastern Colorado completed a mailed questionnaire addressing their health and medical care, insurance coverage, lifestyles, and desire for health education and screening programs. Rural respondents were older and more were self-insured. Twice as many urban men were prompted to participate in the prostate screening program by media announcements (51.0% vs 23.4%), while spouses (21.3% vs 9.4%) and physicians (13.1% vs 6.8%) played greater roles in motivating rural participants. The primary topics for health information and education needs perceived by the rural men were cancer-related, while those for urban men concentrated on cardiac risk factors. Both preferred that this information be provided in the form of written materials or through their personal physicians. This pilot study suggests certain differences in the present health practices, motivational factors, and health information and education needs in urban versus rural men. These differences should be explored further and be considered in the design of cancer prevention and screening programs for these populations.
Age Factors↗