Preferential rod and cone photoreceptor abnormalities in heterozygotes with point mutations in the RDS gene.
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Adult↗
Biomedical subjects
J Bennett
Publications and source records attributed to J Bennett.
High resolution evoked potential imaging of the cortical dynamics of human working memory.
High resolution evoked potentials (EPs), sampled from 115 channels and spatially sharpened with the finite element deblurring method, were recorded from 8 subjects during working memory (WM) and control tasks. The tasks required matching each stimulus with a preceding stimulus on either verbal or spatial attributes. All stimuli elicited a central P200 potential that was larger in the spatial tasks than in the verbal tasks, and larger in the WM tasks than in the control tasks. Frequent, non-matching stimuli elicited a frontal, positive peak at 305 msec that was larger in the spatial WM task relative to the other tasks. Irrespective of whether subjects attended to verbal or spatial stimulus attributes, non-matching stimuli in the WM tasks also elicited an enhanced P450 potential over the left frontal cortex, followed by a sustained potential over the superior parietal cortex. A posterior P390 potential elicited by infrequent, matching stimuli was smaller in amplitude for both spatial and verbal WM tasks compared to control tasks, as was a central prestimulus CNV. These results indicate that WM is a function of a distributed system with both task-specific and task-independent components. Lesion studies and course temporal resolution functional imaging methods, such as PET and fMRI, tend to paint a fairly static picture of the cortical regions which participate in the performance of WM tasks. In contrast, the fine-grain time resolution provided by imaging brain function with EP methods provides a dynamic picture of subsecond changes in the spatial distribution of WM effects over the course of individual trials, as well as evidence for differences in the activity elicited by matching and non-matching stimuli within sequences of trials. This information about the temporal dynamics of WM provides a critical complement to the fine-grain spatial resolution provided by other imaging modalities.
Acoustic Stimulation↗
Five year follow-up of morbidity and mortality among recipients of high-titre measles vaccines in Senegal.
At 3-5 years of age, female recipients of Edmonston-Zagreb high-titre (EZ-HT) and Schwarz high-titre (SW-HT) measles vaccine had lower survival rates than female recipients of Schwarz standard measles vaccine (SW-STD) in Guinea-Bissau, Senegal and Haiti. In Senegal, the children who received high-titre vaccines have now been followed to the age of 5-7 years to determine whether the difference in mortality persisted, and whether differences in vaccine efficacy were apparent. At this age there was no difference in mortality between female recipients of high-titre and standard titre measles vaccines. There was no indication that high-titre EZ-HT vaccine at 5 months (EZ-HT,5m) provided suboptimal protection, as vaccine efficacy after exposure was 97% and 95%, respectively, for EZ-HT,5m and SW-STD,10m vaccines, whereas SW-HT,5m vaccine had an efficacy of 81%. The difference in mortality between recipients of high-titre vaccines and SW-STD observed in several studies during the first few years after vaccination may be explained by non-specific beneficial effects of the standard measles vaccine rather than a harmful effect of the high-titre vaccines.
Female↗
Audit of school entry health assessments: to maximise efficient use of health personnel at school entry assessments at 5 years.
During the last 3 years in which doctors saw all school entrants, the decisions made about each child on examination were recorded and a protocol about decision-making to support children with health needs was drawn up. In September 1994, school entry health care assessments by the school nurses were introduced. Having previously recorded the numbers in each school who required medical interest and support, it was possible to rationalise which schools should be the primary responsibility of the nurses, which should retain medical contact for all children and in which schools assessments should be shared. The outcomes in decision making after introducing nurse assessments were recorded in the same format as used by the doctors, so that the effect of passing responsibility to nurse colleagues could be assessed. The findings suggested that an equivalent number of children were referred to other services or selected for continuing review. However, the proportion of children whose needs were discussed with the headteacher without the children being selected for review was reduced. Issues to take forward were identified.
Child, Preschool↗
Use of the laryngeal mask airway in oral and maxillofacial surgery.
PURPOSE: General anesthesia for the nonintubated oral and maxillofacial surgical patient presents unique anesthetic conditions. The primary concern is the maintenance of an unobstructed airway and protection against aspiration, while minimizing both interference and interruption of the surgical procedure. The laryngeal mask airway is an alternative to the nasal hood for such airway management. The purpose of this article is to inform the oral and maxillofacial surgeon of the clinical relevant information pertaining to the use of the laryngeal mask airway in oral and maxillofacial surgery. Experience with clinical use is discussed.
Anesthesia, Inhalation↗
Four cases of polymorphous low-grade adenocarcinoma.
Since its histologic recognition by the World Health Organization in 1990, polymorphous low-grade adenocarcinoma (PLGA) is now regarded as the second most common salivary gland tumour after mucoepidermoid carcinoma. Distinguishing it from high-grade tumours such as adenoid cystic carcinoma or carcinoma arising within a pre-existing pleomorphic adenoma is important, as PLGA may usually be treated by local excision alone. Any evidence of incomplete marginal clearance, perineural and perivascular spread, and lymph-node involvement is treated with a course of radiotherapy. Follow-up should be for life, and as reported in this series, long-term survival rates are very good, one of our patients surviving for 11 years. The importance of reporting these cases is emphasized.
Adenocarcinoma↗
Photoreceptor cell rescue in retinal degeneration (rd) mice by in vivo gene therapy.
Mutations in the beta subunit of the cGMP phosphodiesterase gene (beta PDE) can cause a recessively inherited retinal degeneration in several species, including mice, dogs and humans. We tested the possibility of altering the course of retinal degeneration in the rd mouse through subretinal injection of a recombinant replication-defective adenovirus that contains the murine cDNA for wild-type (beta PDE, Ad.CMV beta PDE. Subretinal injection of Ad.CMV beta PDE results in beta PDE transcripts and increased PDE activity and delays photoreceptor cell death by six weeks. The findings demonstrate cell rescue by in vivo gene transfer, thus supporting the feasibility of treating an inherited retinal degeneration by somatic gene therapy.
3',5'-Cyclic-AMP Phosphodiesterases↗
Bundling, a newly identified risk factor for neonatal tetanus: implications for global control.
BACKGROUND: Bundling, which consists of wrapping an infant for prolonged periods in a sheepskin cover after dried cow dung is applied, is a common and apparently unique practice limited to the rural, mountainous regions of Northern Pakistan. The practice is initiated at various ages during the neonatal period. Its potential contribution to neonatal tetanus (NNT) had not been evaluated. METHODS: A population-based, matched, case-control study was undertaken to assess bundling and other factors potentially related to NNT in rural parts of the Northern Areas, Pakistan. RESULTS: Bundling instituted within the first 3 days of life was a substantial risk factor for NNT (odds ratio [OR] = 2.5, 95% confidence interval [CI]: 1.3-4.9). Other factors found risky for NNT were delivery on a straw surface and pre-delivery intravaginal application of ghee to the mothers. Handwashing by the delivery attendant and use of a new razor to cut the umbilical cord were protective. CONCLUSIONS: Bundling is a significant risk factor for NNT in the mountainous regions of Northern Pakistan. While this practice is seemingly limited to these remote areas, the findings have broad implications since they indicate that NNT can derive from exposures of the umbilical wound at any time during the first several days of life. Thus, clean cord care at delivery is not itself sufficient to prevent NNT and control programmes need to address post-delivery sources of NNT.
Age of Onset↗
A novel simian virus 40 early-region domain mediates transactivation of the cyclin A promoter by small-t antigen and is required for transformation in small-t antigen-dependent assays.
At least three regions of the simian virus 40 small-t antigen (small-t) contribute to the protein's ability to enhance cellular transformation. As we showed previously for rat F111 cells, one region includes sequences from residues 97 to 103 that are involved in the binding and inhibition of protein phosphatase 2A. In the present study, the role of the protein phosphatase 2A binding region was confirmed in two additional small-t-dependent transformation systems. Second, small-t was found to provide a function previously identified as a large-T transformation domain. Mutations in residues 19 to 28 of large-T affected its transforming ability, but these mutations were complemented by a wild-type small-t. A third region of small-t was also required for efficient transformation. This region, the 42-47 region, is shared by large-T and small-t and contains a conserved HPDKGG hexapeptide. The 42-47 region function could be provided by either small-t or large-T in small-t-dependent systems. Mutations in the 42-47 region reduced the ability of small-t to transactivate the cyclin A promoter, of interest because small-t increased endogenous cyclin A mRNA levels in both human and monkey cells, as well as transactivating the promoter in transient assays.
Animals↗
A cross sectional study of the independent effect of occupation on lung function in British coal miners.
BACKGROUND: Chronic bronchitis and emphysema are now recognised complications of occupational exposure to coal dust, and since 1992 compensation has been available for miners with impaired lung function provided that they also have x ray film evidence of pneumoconiosis. However, many miners with heavy exposure to coal dust and impairment of lung function therefore do not qualify for compensation because they do not have simple pneumoconiosis. In the present study attempts were made to determine whether coal mining is an independent risk factor for impairment of lung function in a group of Nottinghamshire miners with no evidence of simple pneumoconiosis, by comparing these men with a group of local controls who were not occupationally exposed. METHOD: Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were obtained on 1286 miners with no evidence of pneumoconiosis on x ray film. Lung function data were also obtained from a random sample of 567 men aged between 40 and 70 living in a district of Nottingham and who had never worked in the mining industry or in any other dusty occupation. Multiple linear regression in SPSS was used to estimate the mean independent effect of mining on FEV1 and FVC after adjustment for age, height, and smoking, in all miners and controls, and in a subgroup of men of 45 and under. In men of 45 and under, the independent effects of mining and smoking on the probability of a deficit of one litre or more from modelled predicted FEV1 values were computed with logistic regression in EGRET. RESULTS: There was a significant mean effect of mining on FEV1 after adjustment for age, height, and smoking of -155 ml (95% confidence interval (95% CI) -74 to -236 ml, P < 0.001), but the size of effect was inversely related to age such that in men of 45 and under the estimated mean effect of mining was -251 ml (95% CI -140 to -361 ml, P < 0.001). In this subgroup of younger men, 4.7% of miners and 0.7% of controls had a deficit of one litre or more from predicted FEV1 values, and in logistic regression, there was a marginally significant independent effect of both smoking (P = 0.05) and mining (P = 0.07) for a deficit of this magnitude. CONCLUSIONS: Occupational exposure to coal dust is associated with a small mean deficit in lung function even in the absence of simple pneumoconiosis, and independently from the effects of smoking. The requirement that miners should have evidence of pneumoconiosis to qualify for compensation for impaired lung function is therefore unjustified.
Adult↗
The effect of inhaled heparin on bronchial reactivity to sodium metabisulphite and methacholine in patients with asthma.
Inhaled heparin inhibits the early response to allergen and exercise-induced asthma, probably by inhibiting mast cell mediator release. Recent animal studies suggest that heparin might also inhibit cholinergic neurotransmission in asthma by restoring inhibitory M2 receptor function. We have tested the hypothesis that heparin inhibits neurally-mediated bronchoconstriction in asthma by examining the effect of inhaled heparin on bronchial reactivity to sodium metabisulphite. We also examined the effect of inhaled heparin on methacholine-induced bronchoconstriction to exclude a direct effect on airway smooth muscle. Eleven patients with mild asthma inhaled nebulized heparin (1,000 U.kg-1) or placebo (normal saline) in a randomized, double-blind fashion, 10 min before a challenge with sodium metabisulphite. Nine patients were also challenged with methacholine after the same dose of heparin or placebo. Inhaled heparin did not significantly change forced expiratory volume in one second (FEV1), nor did it alter the provocative dose of sodium metabisulphite or methacholine required to cause a 20% fall in FEV1 (PD20). Geometric mean sodium metabisulphite PD20 was 2.54 and 2.15 mumol after placebo and heparin, respectively (mean difference -0.24 doubling doses; 95% confidence interval (95% CI) -0.64-0.17). Geometric mean methacholine PD20 was 1.00 and 1.51 mumol after placebo and heparin, respectively (mean difference 0.6 doubling doses; 95% CI -0.25-1.5). Thus, heparin inhaled at doses sufficient to inhibit allergen and exercise-induced bronchoconstriction has no effect on the response to sodium metabisulphite and methacholine challenge in asthma. This argues against an inhibitory effect on neural pathways or airway smooth muscle.
Administration, Inhalation↗
Preventing AIDS through song. Interview by Gay Williams.
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Community Health Nursing↗
Performance and potency of tetanus toxoid: implications for eliminating neonatal tetanus.
Neonatal tetanus (NT) is a major cause of mortality in developing countries, with over 400,000 deaths estimated to occur annually. WHO has adopted the goal of eliminating NT worldwide, and a major strategy for its prevention is the administration of at least two properly spaced doses of tetanus toxoid (TT) to women of childbearing age in high-risk areas to protect passively their newborns at birth. In certain countries the locally produced TT vaccine has been shown to be subpotent, while other countries have reported NT among infants born to vaccinated women. An extensive review of production and quality control procedures was carried out between 1993 and 1995 in 8 of 22 TT-producing countries that also report NT cases, with a more superficial assessment being carried out in the remaining 14 countries. Only 4 of the 22 countries have a functioning national control authority to monitor TT production and vaccine quality. A total of 80 TT lots from 21 manufacturers in 14 of the 22 NT-reporting countries were tested for potency. Of these, 15 lots from eight manufacturers in seven countries had potency values below WHO requirements. TT potency can also be compromised by improper vaccine handling. To eliminate neonatal tetanus worldwide requires assurance that all doses of TT meet WHO production and quality requirements and that the field effectiveness of TT is monitored through systematic NT case investigations and assessment of coverage.
Adolescent↗
Rhinolith in a patient with cleft palate: a case report.
Dental anomalies are well documented in patients with cleft palate, although reports of intranasal teeth in these patients are extremely rare. This paper discusses the case of a rhinolith associated with tooth-like structures in a patient with a treated cleft palate.
Adult↗
Sequence analysis of the 5.34-kb 5' flanking region of the human rhodopsin-encoding gene.
In order to define elements which may be involved in regulating human rhodopsin expression, we have isolated and sequenced a clone containing 5.34 kb of the 5'-upstream region of the human rhodopsin-encoding gene. The 5.34-kb human segment contains multiple potential transcription factor-binding sites and a subfamily of Alu repeats. The same subfamily of Alu repeats is found 5.8 kb upstream from the human red/green visual pigment-encoding gene.
Animals↗
In vivo and in vitro studies on the neurotoxic potential of 6-hydroxydopamine analogs.
In an attempt to determine which physical and biological properties could best be correlated with neurotoxic potential, seven analogs of 1-(2,4,5-trihydroxyphenyl)-2-aminoethane (1), better known as 6-hydroxydopamine, were synthesized and compared to 1 in a variety of ways both in vivo and in vitro. The analogs, in combination with the standard 1, include all eight of the 2,4,5-trisubstituted-phenyl derivatives of phenethylamine and alpha-methylphenethylamine in which the substitution is of the trihydroxy or aminodihydroxy form. Low (60 nmol) and high (300 nmol) intracerebroventricular doses of all analogs produced long-term (7 day) reduction of mouse whole brain norepinephrine (NE) and lesser depletions of dopamine (DA), and effects on serotonin were varied. The analog 1-(5-amino-2,4-dihydroxyphenyl)-2-aminopropane (8) was both more complete and more selective than the standard 1 in depleting NE. Using a histofluorometric glyoxylic acid method and Fink-Heimer silver degeneration stain, it was determined that overt neural degeneration was produced by 8. In vitro, the ease of oxidation of the eight analogs was found to be represented by a formal potential range of -130 to -212 mV vs SCE. However, there was no obvious relationship between ease of oxidation and the extent of monoamine depletion from mouse brain. Using kinetic analysis of synaptosomal accumulation of [3H]NE and [3H]DA, it was found that the standard 1 is more potent in its interaction with the DA uptake site (Ki = 12 +/- 0 microM) than the NE uptake site (Ki = 51 +/- 1 microM). A correlation analysis was used to determine that differences in NE and DA depletion by each analog could not be explained by differences in potency for in vitro uptake blockade. However, there was a correlation between the Ki for [3H]NE uptake blockade and the EC50 for synaptosomal release of preloaded [3H]NE for the eight analogs (R2 = 0.96; for log:log plot, R2 = 0.54), indicating that the results for these two in vitro tests both reflect interaction with the same NE neuronal membrane transport site. A similar correlation between Ki and EC50 was shown for all eight analogs using [3H]DA (R2 = 0.92; for log:log plot, R2 = 0.52), indicating interaction with the same DA neuronal membrane transport site. These findings demonstrate that there is no single property that can account for selectivity of action and/or potency of catecholamine neurotoxins related to 6-hydroxydopamine.
Animals↗
IL-12 prevents mortality in mice infected with Histoplasma capsulatum through induction of IFN-gamma.
Histoplasma capsulatum is a pathogenic fungus found in discrete geographic locations throughout the world. The fungus invades the reticuloendothelial organs such as the spleen and liver of immunocompetent hosts where it is usually controlled. However, in individuals with immune deficiency, histoplasmosis is a severe and potentially fatal disease. Resistance to this infection is due primarily to a cellular immune response mediated by T cells and macrophages. Moreover, IFN-gamma is critical in activating macrophages to kill the organism. Herein we study the regulation of cytokine induction in mice infected with H. capsulatum and the effects of IL-12 in the course of infection. Mice infected with H. capsulatum and treated with neutralizing Abs to IFN-gamma, TNF-alpha, or IL-12 experienced accelerated mortality, indicating that endogenous production of these cytokines plays an important role in response to infection. In contrast, mice treated with IL-12 or a neutralizing Ab to IL-4 at the initiation of infection had substantially diminished mortality. Moreover, mice infected and treated with IL-12 show a two- to threefold increase in the amount of IFN-gamma following in vitro stimulation with specific H. capsulatum Ag compared with the control infected mice. The protective effect of IL-12 could be abrogated if a neutralizing Ab to IFN-gamma was given at the same time, demonstrating that the role of IL-12 in protection was mediated by IFN-gamma. Additionally, infected mice treated with IL-12 had a severalfold decrease in the colony counts of H. capsulatum in spleen cells after 5 days of infection as compared with control animals. Lastly, spleen cells from infected animals treated with IL-12 showed a striking decrease in their proliferative response to mitogen or H. capsulatum Ag. Responses could be restored by adding inhibitors of IFN-gamma or of nitric oxide to the in vitro cultures. The above observations suggest that IL-12 may be useful in immunologic intervention against this opportunistic pathogen.
Animals↗
Characterization of a DNA sequence that detects repetitive DNA elements in the Asian rice gall midge (Orseolia oryzae) genome: potential use in DNA fingerprinting of biotypes.
We have isolated based on reverse genome hybridization, and sequenced a DNA clone, pNZE25, from a partial genomic library of the Asian rice gall midge Orseolia oryzae (Wood-Mason) (O.o.). Clone pNZE25 is highly A+T rich (67%), lacks any open reading frame and does not display homology to sequences in GenBank. Clone pNZE25 detects a 120-bp repeat in the O.o. genome, as seen from the generation of a 120-bp ladder after Southern analysis of HinfI-digested genomic DNA. When used to probe O.o. genomic DNA digested with DraI, HaeIII or AluI, pNZE25 generates individual specific DNA fingerprints on target DNA isolated from gall midge biotypes collected from different parts of India.
Animals↗