Malignant peripheral nerve sheath tumour of the tongue.
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Adult↗
Biomedical subjects
M Baldwin
Publications and source records attributed to M Baldwin.
Maternal anxiety and attitudes to universal neonatal hearing screening.
Neonatal hearing screening of all babies within the maternity unit is now feasible using transient evoked otoacoustic emission (TEOAE) recording. However, in many maternity units in the United Kingdom, the majority of babies are discharged within the first 48 hours. During the first two days of life, there is a higher proportion of babies in whom emissions cannot be recorded. A universal TEOAE hearing screen has been implemented in Whipps Cross Hospital. As 70% of the babies are discharged from the maternity unit before they are 48 hours old, a two stage screen was implemented, with failure at the initial TEOAE test being followed by a retest after 4-6 weeks. The maternal anxiety caused by this model was investigated in 288 mothers enrolled for the initial TEOAE test. Generally, anxiety was low and attitudes towards the screen were positive. Ninety-seven per cent of mothers considered the screen to be worthwhile at the initial test with 15% feeling it had caused some anxiety but less than 1% being very worried. The mothers who had some anxieties were not dissatisfied with the screen, and within this group there was no increase in the proportion of babies who had failed the initial test. At the retest, two of 57 mothers (3.5%) considered they were very worried, but there was no significant deterioration in attitude towards the screen. Spielberger's State-Trait Anxiety Inventory revealed no significant difference in the anxiety state of the retest group when compared with a control group whose babies had not received a neonatal hearing test. The results of the initial test and the retest did not influence the anxiety state of the mothers. Ways of minimizing anxiety caused to a minority of mothers whilst maintaining positive attitudes to the screen are discussed.
Anxiety↗
Early manifestations of manganese neurotoxicity in humans: an update.
It is possible to detect early signs of neurotoxic dysfunction associated with occupational and environmental exposure to manganese; neurophysiologic and neurobehavioral tests can be used in the absence of clinical manifestations. Although outcomes from individual studies vary, they collectively show a pattern of slowing motor functions, increased tremor, reduced response speed, enhanced olfactory sense, possible memory and intellectual deficits, and mood changes. This overall portrait is consistent with the action of manganese on the central nervous system. In reports to date, there is little consistency in dose-effect relationships between internal parameters of manganese exposure (blood manganese, urinary manganese, hair manganese) and external measures and neurologic outcomes. Several studies suggest the existence of dose-effect relationships, but additional clarification is needed.
Environmental Exposure↗
The effects of two types of cognitive tasks on postural stability in older adults with and without a history of falls.
BACKGROUND: This study used a dual task design to investigate the effects of two different types of cognitive tasks on stability (as measured by center of pressure displacement) in young vs older adults with and without a history of falls. METHODS: Two secondary cognitive tasks, a sentence completion and a visual perceptual matching task, were used to produce changes in attention during quiet stance under flat vs compliant surface conditions in 20 healthy young adults, 20 healthy older adults, and 20 older adults with a history of imbalance and falls. Postural stability was quantified using forceplate measures of center of pressure (COP). Speed and accuracy of verbal response on the cognitive tasks were also quantified. RESULTS: During the simultaneous performance of a cognitive and postural task, decrements in performance were found in the postural stability measures rather than the cognitive measures for all three groups. While no differences were found between the young adults and the older healthy adults on the firm surface, no task condition, when task complexity was increased (either through the introduction of a secondary cognitive task, or a more challenging postural condition such as standing on the compliant surface), significant differences in postural stability between the two groups became apparent. In contrast to the young and healthy older adults, postural stability in older adults with a history of falls was significantly affected by both cognitive tasks. CONCLUSION: Results suggest that when postural stability is impaired, even relatively simple cognitive tasks can further impact balance. Results further suggest that the allocation of attention during the performance of concurrent tasks is complex; depending on many factors including the nature of both the cognitive and postural task, the goal of the subject and the instructions.
Accidental Falls↗
The effect of multidimensional exercises on balance, mobility, and fall risk in community-dwelling older adults.
BACKGROUND AND PURPOSE: This prospective clinical investigation examined the effects of a multidimensional exercise program on balance, mobility, and risk for falls in community-dwelling older adults with a history of falling. Factors used to predict adherence and a successful response to exercise were identified. SUBJECTS: A total of 105 community-dwelling older adults (> or = 65 years of age) with a history of two or more falls in the previous 6 months (no neurologic diagnosis) participated. They were classified into (1) a control group of fallers (n = 21), (2) a fully adherent exercise group (n = 52), and (3) a partially adherent exercise group (n = 32). METHODS: Following evaluation, each patient received an individualized exercise program addressing the impairments and functional disabilities identified during the assessment. The control group received no intervention. Changes in performance on five clinical tests of balance and mobility and fall risk were compared among groups. RESULTS: Both exercise groups scored better than the control group on all measures of balance and mobility. Although both exercise groups showed a reduction in fall risk compared with the control group, the greatest reduction was found in the fully adherent exercise group. Factors associated with successful response to exercise included degree of adherence to exercise program and pretest score on the Tinetti Mobility Assessment. CONCLUSION AND DISCUSSION: Exercise can improve balance and mobility function and reduce the likelihood for falls among community-dwelling older adults with a history of falling. The amount of exercise needed to achieve these results, however, could not be determined from this study.
Accidental Falls↗
Predicting the probability for falls in community-dwelling older adults.
BACKGROUND AND PURPOSE: The objective of this retrospective case-control study was to develop a model for predicting the likelihood of falls among community-dwelling older adults. SUBJECTS: Forty-four community-dwelling adults (> or = 65 years of age) with and without a history of falls participated. METHODS: Subjects completed a health status questionnaire and underwent a clinical evaluation of balance and mobility function. Variables that differed between fallers and nonfallers were identified, using t tests and cross tabulation with chi-square tests. A forward stepwise regression analysis was carried out to identify a combination of variables that effectively predicted fall status. RESULTS: Five variables were found to be associated with fall history. These variables were analyzed using logistic regression. The final model combined the score on the Berg Balance Scale with a self-reported history of imbalance to predict fall risk. Sensitivity was 91%, and specificity was 82%. CONCLUSION AND DISCUSSION: A simple predictive model based on two risk factors can be used by physical therapists to quantify fall risk in community-dwelling older adults. Identification of patients with a high fall risk can lead to an appropriate referral into a fall prevention program. In addition, fall risk can be used to calculate change resulting from intervention.
Accidental Falls↗
High-level expression and characterization of a purified 142-residue polypeptide of the prion protein.
The major, and possible only, component of the infectious prion is the scrapie prion protein (PrPSc); the protease resistant core of PrPSc is PrP 27-30, a protein of approximately 142 amino acids. PrPSc is derived from the cellular PrP isoform (PrPC) by a post-transliatonal process in which a profound conformational change occurs. Syrian hamster (SHa) PrP genes of varying length ranging from the N- and C- terminally truncated 90-228 up to the full-length mature protein 23-231 were inserted into various secretion and intracellular expression vectors that were transformed into Escherichia coli deficient for proteases. Maximum expression was obtained for a truncated SHaPrP containing residues 90-231, which correspond to the sequence of PrP 27-30; disruption of the bacteria using a microfluidizer produced the highest yields of this protein designated rPrP. After solubilization of rPrP in 8 M GdnHC1, it was purified by size exclusion chromatography and reversed phase chromatography. During purification the recovery was approximately 50%, and from each liter of E. coli culture, approximately 50 mg of purified rPrP was obtained. Expression of the longer species containing the basic N-terminal region was less successful and was not pursued further. The primary structure of rPrP was verified by Edman sequencing and mass spectrometry, and secondary structure determined by circular dichroism and Fourier transform infrared spectroscopy. When rPrP was purified under reducing conditions, it had a high beta-sheet content and relatively low solubility similar to PrPSc, particularly at pH values > 7. Refolding of rPrP by oxidation to form a disulfide bond between the two Cys residues of this polypeptide produced a soluble protein with a high alpha-helical content similar to PrPC. These multiple conformations of rPrP are reminiscent of the structural plurality that characterizes the naturally occurring PrP isoforms. The high levels of purified rPrP which can now be obtained should facilitate determination of the multiple tertiary structures that Prp can adopt.
Amino Acid Sequence↗
Solid-state NMR studies of the prion protein H1 fragment.
Conformational changes in the prion protein (PrP) seem to be responsible for prion diseases. We have used conformation-dependent chemical-shift measurements and rotational-resonance distance measurements to analyze the conformation of solid-state peptides lacking long-range order, corresponding to a region of PrP designated H1. This region is predicted to undergo a transformation of secondary structure in generating the infectious form of the protein. Solid-state NMR spectra of specifically 13C-enriched samples of H1, residues 109-122 (MKHMAGAAAAGAVV) of Syrian hamster PrP, have been acquired under cross-polarization and magic-angle spinning conditions. Samples lyophilized from 50% acetonitrile/50% water show chemical shifts characteristic of a beta-sheet conformation in the region corresponding to residues 112-121, whereas samples lyophilized from hexafluoroisopropanol display shifts indicative of alpha-helical secondary structure in the region corresponding to residues 113-117. Complete conversion to the helical conformation was not observed and conversion from alpha-helix back to beta-sheet, as inferred from the solid-state NMR spectra, occurred when samples were exposed to water. Rotational-resonance experiments were performed on seven doubly 13C-labeled H1 samples dried from water. Measured distances suggest that the peptide is in an extended, possibly beta-strand, conformation. These results are consistent with the experimental observation that PrP can exist in different conformational states and with structural predictions based on biological data and theoretical modeling that suggest that H1 may play a key role in the conformational transition involved in the development of prion diseases.
Amino Acid Sequence↗
Expression of HIV regulatory and structural mRNA in the central nervous system.
OBJECTIVE: HIV encephalitis is observed in approximately one-half of AIDS autopsies. Although most investigators would agree that central nervous system (CNS) macrophages are the predominant infected cell in HIV encephalitis, there remains some controversy regarding whether other CNS cells can be infected by HIV and thus show the molecular characteristics of such an infection. DESIGN AND METHODS: Using reverse transcriptase polymerase chain reaction (PCR) and immunocytochemistry (ICC), we examined CNS tissues from AIDS and control autopsies for the presence of non-productive HIV infection. RESULTS: Single-spliced mRNA for structural envelope proteins were detected in the basal ganglia of only one of nine HIV-seropositive autopsies without HIV encephalitis and none of five seronegative autopsy controls. Double-spliced mRNA for regulatory proteins (e.g., Nef and Tat) were not detected in either the seropositive non-HIV encephalitis or seronegative controls. Both single and double-spliced viral RNA could be detected in basal ganglia of 10 out of 13 autopsies with HIV encephalitis. Similar findings were obtained when cerebral white matter was examined. Using PCR primers that distinguish single from double-spliced mRNA, we found no evidence for selective expression of the Nef regulatory gene. CONCLUSIONS: These data suggest that expression of HIV mRNA in the CNS is limited to those patients with HIV encephalitis. Further HIV encephalitis appears to be a chronic permissive infection of the CNS, without evidence of restricted Nef transcript expression.
Acquired Immunodeficiency Syndrome↗
The snakestone experiments. An early modern medical debate.
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Animals↗
Sclerosing lobular hyperplasia of the breast: imaging features in 15 cases.
OBJECTIVE: Sclerosing lobular hyperplasia is an infrequent benign lesion of the breast, defined as prominent hyperplasia of the lobules with sclerosis of the interlobular stroma. It commonly presents as a tumorlike mass clinically. Sclerosing lobular hyperplasia has been identified at biopsy at our institution with rare but increasing frequency. We reviewed the imaging features of 15 patients with biopsy-proven sclerosing lobular hyperplasia to determine if a characteristic imaging pattern could suggest this diagnosis. MATERIALS AND METHODS: The mammograms and sonograms of all women with pathologically proved sclerosing lobular hyperplasia seen between January 1986 and June 1993 were retrospectively reviewed by two of the authors who were familiar with the pathologic diagnosis. Imaging findings that led to biopsy or were present on the preoperative studies were reviewed. The study included 15 patients ranging in age from 21 to 46 years old, with a mean age of 32 years. Seven were black, and eight were white. All women had mammograms, three patients had prior mammograms for comparison, and sonography was done in all but one case. Presenting symptoms included a recently discovered breast lump in eight patients, breast tenderness in one patient, and a clear nipple discharge in one patient. The other five were asymptomatic and had screening mammograms. RESULTS: Eight patients (53%) had a well-defined mass on mammography, varying in size from 1.0 cm to 8.0 cm (mean, 3.7 cm). In one of these patients, the nodule was proved to be a fibroadenoma; sclerosing lobular hyperplasia was found only microscopically. Microcalcifications were present within the mass on mammography in one patient. Mammograms in two women showed asymmetric increased density compared with the opposite breast, and in five cases, the mammographic findings were interpreted as normal. Sonograms showed a solid, well-defined mass with either homogeneous or mixed echoes in 10 of 14 patients (71%). In only one of these nodules was acoustic enhancement present. In the other four women, sonograms were normal. No characteristic findings were identified that would suggest sclerosing lobular hyperplasia as a likely diagnosis preoperatively, and, in fact, in many cases a diagnosis of fibroadenoma was considered most probable. CONCLUSION: The imaging findings of sclerosing lobular hyperplasia are not sufficiently characteristic to distinguish the lesion from fibroadenomas and well-circumscribed carcinomas.
Adult↗
The views of parents of hearing impaired children on the need for neonatal hearing screening.
Much research is now being undertaken into the implementation of universal neonatal hearing screens, but consumer opinion about such screening has not been widely available. The opinions of the parents of 356 children and young adults, with varying degrees of permanent hearing impairment were sought for the current study. They were questioned about their satisfaction with the age at which the hearing impairment was confirmed to be present in their child. Of 208 responses, only 58 were reasonably satisfied with the age at which their child's impairment had been confirmed. They were also asked whether they would have wanted a neonatal hearing screen had it been available. The overwhelming majority (166) would have welcomed such a test. This opinion was shared by the parents, even when their child had a mild or unilateral impairment. Parental comments about the advantages and disadvantages of neonatal screening are discussed.
Adolescent↗
Structural clues to prion replication.
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Animals↗
Nervous system dysfunction among workers with long-term exposure to manganese.
Neurological disorders, bearing many similarities to Parkinson's disease, have been associated with environmental and occupational exposure to manganese (Mn). To document early nervous system dysfunction associated with long-term exposure to Mn, a battery of neurofunctional tests was administered to workers employed in Mn alloy production. Study participation was 95% (n = 115). A matched pair design was used; actively working men, with no history of workplace exposure to neurotoxins, were recruited from the region as referents. Matching was done on the variables: age (+/- 3 years), educational level (+/- 2 years), smoking status, and number of children. Stationary environmental sampling indicated that Mn levels varied widely (geometric means: Mn dust, 0.89 mg/m3; respirable Mn, 0.04 mg/m3). The alloy workers had significantly higher levels of whole blood Mn (geometric mean: 1.03 microgram/100 ml vs 0.68 microgram/100 ml); no differences were observed for urinary Mn. Univariate analysis (paired t test, Signed Rank and McNemar) and multivariate analysis of variance (Hotelling-Lawley statistic) revealed that the pairs differed on symptom reporting, emotional state, motor functions, cognitive flexibility, and olfactory perception threshold; verbal fluency, basic mathematics, reading capability, and attentional capacity were similar. These findings are consistent with current knowledge on brain Mn activity and suggest that manifestations of early manganism can be observed in well designed population studies, using sensitive testing methods.
Adult↗
Conversion of alpha-helices into beta-sheets features in the formation of the scrapie prion proteins.
Prions are composed largely, if not entirely, of prion protein (PrPSc in the case of scrapie). Although the formation of PrPSc from the cellular prion protein (PrPC) is a post-translational process, no candidate chemical modification was identified, suggesting that a conformational change features in PrPSc synthesis. To assess this possibility, we purified both PrPC and PrPSc by using nondenaturing procedures and determined the secondary structure of each. Fourier-transform infrared (FTIR) spectroscopy demonstrated that PrPC has a high alpha-helix content (42%) and no beta-sheet (3%), findings that were confirmed by circular dichroism measurements. In contrast, the beta-sheet content of PrPSc was 43% and the alpha-helix 30% as measured by FTIR. As determined in earlier studies, N-terminally truncated PrPSc derived by limited proteolysis, designated PrP 27-30, has an even higher beta-sheet content (54%) and a lower alpha-helix content (21%). Neither PrPC nor PrPSc formed aggregates detectable by electron microscopy, while PrP 27-30 polymerized into rod-shaped amyloids. While the foregoing findings argue that the conversion of alpha-helices into beta-sheets underlies the formation of PrPSc, we cannot eliminate the possibility that an undetected chemical modification of a small fraction of PrPSc initiates this process. Since PrPSc seems to be the only component of the "infectious" prion particle, it is likely that this conformational transition is a fundamental event in the propagation of prions.
Animals↗
The connection between individual responsibility and mammography.
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Attitude to Health↗
Ascaris lumbricoides resulting in acute cholecystitis and pancreatitis in the Midwest.
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Acute Disease↗
The clinical application of oto-acoustic emissions in paediatric audiological assessment.
The value of otoacoustic emissions as an objective screening test for normal peripheral auditory function in infants is currently the subject of extensive and promising research. Additionally the measurement of cochlear emissions is potentially useful when children cannot be tested reliably by traditional subjective methods but confirmation of normal hearing is diagnostically important. Three groups of children are described who present such audiological dilemmas: children with non-organic hearing loss, children with severe learning difficulties and more rarely children with an abnormal auditory brainstem response who also have damage to the central nervous system. In all three groups otoacoustic emission testing was found to be diagnostically useful in determining normal peripheral auditory function thereby resolving some of the dilemmas facing paediatric audiology and ENT clinics.
Adolescent↗