PubMed Health⌕ Search

Biomedical subjects

R Meehan

Publications and source records attributed to R Meehan.

18 recordsLinked to original sources
PubMed2006

Prevalence and risk factors of neurological disability and impairment in children living in rural Kenya.

BACKGROUND: There is little data on the burden of neurological impairment (NI) in developing countries, particularly in children of Africa. METHODS: We conducted a survey of NI in children aged 6-9 years in a rural district of Kenya. First, we screened for neurological disability by administering the Ten Questions Questionnaire (TQQ) to parents/guardians of children in a defined population. In phase two, we performed a comprehensive clinical and psychological assessment on children who tested positive on TQQ and on a similar number of children who tested negative. RESULTS: A total of 10 218 children were screened, of whom 955 (9.3%) were positive on TQQ. Of these, 810 (84.8%) were assessed, and of those who tested negative 766 (8.3%) were assessed. The prevalence for moderate/severe NI was 61/1000 [95% confidence interval (95% CI) 48-74]. The most common domains affected were epilepsy (41/1000), cognition (31/1000), and hearing (14/1000). Motor (5/1000) and vision (2/1000) impairments were less common. Of the neurologically impaired children (n = 251), 56 (22%) had more than one impairment. Neonatal insults were found to have a significant association with moderate/severe NI in both the univariate [odds ratio (OR) = 1.70; 95% CI 1.12-2.47] and multivariate analyses (OR = 1.30; 95% CI 1.09-1.65). CONCLUSIONS: There is a considerable burden of moderate/severe NI in this area of rural Kenya, with epilepsy, cognition, and hearing being the most common domains affected. Neonatal insults were identified as an important risk factor.

Child↗
PubMed2005

A mechanism of injury to the forefoot in car crashes.

OBJECTIVE: The purpose of this study was to determine a mechanism of injury of the forefoot due to impact loads and accelerations as noted in some frontal offset car crashes. METHODS: The impact tests conducted simulated knee-leg-foot entrapment, floor pan intrusions, whole-body deceleration, muscle tension, and foot/pedal interaction. Specimens were impacted at speeds of up to 16 m/s. To verify this injury mechanism research was conducted in an effort to produce Lisfranc type injuries and metatarsal fractures. A total of 54 lower legs of post-mortem human subjects were tested. Two possible mechanisms of injury were investigated. For the first mechanism the driver was assumed to be braking hard with the foot on the brake pedal and at 0 deg plantar flexion (Plantar Nominal Configuration) and the brake pedal was in contact with the foot behind the ball of the foot. The second mechanism was studied by having the ball of the foot either on the brake pedal or on the floorboard with the foot plantar-flexed 35 to 50 deg (Plantar Flexed Configuration). RESULTS: The Plantar Nominal injury mechanism yielded few injuries of the type the study set out to produce. Out of 13 specimens tested at speeds of 16 m/s, three had injuries of the metatarsal (MT) and tarsometatarsal joints. The Plantar Flexed Configuration injury mechanism yielded 65% injuries at high (12.5-16 m/s) and moderate (6-12 m/s) speeds. CONCLUSION: It is concluded that Lisfranc type foot injuries are the result of impacting the forefoot in the Plantar Flexed Configuration. The injuries were consistent with those reported by physicians treating accident victims and were verified by an orthopedic surgeon during post impact x-ray and autopsy. They included Lisfranc fractures, ligamentous disruptions, and metatarsal fractures.

Accidents, Traffic↗
PubMed2003

Gene expression in the developing embryo and fetus.

Determining the stage- and tissue-specific patterns of gene expression shown by the embryo and fetus will provide information about the control of normal development. Identification of alterations in these patterns associated with specific abnormal phenotypes will also be informative regarding the underlying molecular mechanisms. In addition, qualitative and quantitative changes in gene expression that deviate from the norm may provide a potential marker system for predicting future developmental defects, a system that would be particularly useful in preimplantation embryo technologies before recipient transfer. However, there are a number of important issues regarding the interpretation and relevance of many gene expression studies currently undertaken that are often not considered or are ignored. Even when rigorous methodology is applied to detect differences in gene expression, their functional significance is rarely defined. This review discusses the relevance of gene expression changes as diagnostic markers in relation to protein and epigenetic changes and indicates that gene expression studies should be rigorously designed and interpreted to yield meaningful results.

Animals↗
PubMed1998

Management of frontal sinus fractures with posterior table involvement: a retrospective study.

Management of frontal sinus fracture has been a matter of debate. Combined fractures of the anterior and posterior walls have been managed by various techniques, including observation, open reduction and internal fixation, ablation, obliteration, and, most recently, cranialization. The earlier techniques have met with frequent complications, including sinusitis, mucopyocele, cerebrospinal fluid leak, meningitis, and brain abscess, along with various chronic pain symptoms. Cranialization of the frontal sinus was first introduced for injuries of both walls with intracranial penetration. From 1990 to 1996, frontal sinus fractures of 11 patients (10 men and 1 woman) were treated using the cranialization procedure. Based on patient history, clinical findings, radiographic diagnoses, operative techniques, and follow-ups of these patients the authors conclude that cranialization of the frontal sinus is a safe and effective method of treating posterior table frontal sinus fractures.

Accidents, Traffic↗
PubMed1996

Metastatic disease in the cerebellum. The LSU experience in 1981-1993.

We retrospectively determined the outcome of management of metastatic disease in the cerebellum (MDC) in 45 patients because MDC is considered to be more immediately life-threatening than metastases in other intracranial locations. Treatment consisted of tumor resection and radiotherapy (RR; n = 11) or of radiotherapy alone (RA; n = 34). Significant differences in the median survival (15 months for RR and 3 months for RA, p = 0.005) and in survival rates at 1 year (61 +/- 30% for RR and 9 +/- 10% for RA, p < 0.001) and at 2 years (15 +/- 22% for RR and 0% for RA, p < 0.05) were noted. This combined management program of surgery followed by radiotherapy for MDC produced a worthwhile gain in survival.

Aged↗
PubMed1995

Studies of DNA methylation in animals.

We have been studying the evolution and function of DNA methylation in vertebrate animals using three related approaches. The first is to further characterise proteins that bind to methylated DNA. Such proteins can be viewed as 'receptors' of the methyl-CpG 'ligand' that mediate downstream consequences of DNA modification. The second approach involves CpG islands. These patches of non-methylated DNA coincide with most gene promoters, but their origin and functional significance have only recently become the subject of intensive study. The third approach is to trace the evolution of DNA methylation. Genomic methylation patterns of vertebrates are strikingly different from those of invertebrates. By studying methylation in animals that diverged from common ancestors near to the invertebrate/vertebrate boundary, we will assess the possibility that changes in DNA methylation contributed causally to the evolution of the complex vertebrate lineage.

Animals↗
PubMed1993

The role of psychoneuroendocrine factors on spaceflight-induced immunological alterations.

This paper summarizes previous in-flight infections and novel conditions of spaceflight that may suppress immune function. Granulocytosis, monocytosis, and lymphopenia are routinely observed following short duration orbital flights. Subtle changes within the monocyte and T cell populations can also be noted by flow cytometric analysis. The similarity between the immunological changes observed after spaceflight and other diverse environmental stressors suggest that most of these alterations may be neuroendocrine-mediated. Available data support the hypothesis that spaceflight and other environmental stressors modulate normal immune regulation via stress hormones, other than exclusively glucocorticoids. It will be essential to simultaneously collect in-flight endocrine, immunologic, and infectious illness data to determine the clinical significance of these results. Additional research that delineates the neuroendocrine mechanisms of stress-induced changes in normal immune regulation will allow clinicians in the future to initiate prophylactic immunomodulator therapy to restore immune competence altered by the stress of long-duration spaceflight and therefore reduce morbidity from infectious illness, autoimmune disease, or malignancy.

Humans↗
PubMed1992

Transcriptional repression by methylation of CpG.

Methylated DNA in mammals is associated with transcriptional repression and nuclease resistant chromatin. In this review we discuss how these effects may be mediated by proteins that bind to methylated DNA.

Animals↗
PubMed1990

A nuclear protein that binds preferentially to methylated DNA in vitro may play a role in the inaccessibility of methylated CpGs in mammalian nuclei.

The effects of DNA methylation on gene expression and chromatin structure suggest the existence of a mechanism in the nucleus capable of distinguishing methylated and non-methylated sequences. We report the finding of a nuclear protein in several vertebrate tissues and cell lines that binds preferentially to methylated DNA in vitro. Its lack of sequence-specific requirements makes it potentially capable of binding to any methylated sequence in mammalian nuclei. An in vivo counterpart of these results is that methylated CpGs are inaccessible to nucleases within nuclei. In contrast, non-methylated CpG sites, located mainly at CpG islands, and restriction sites not containing this dinucleotide, are relatively accessible. The possibility that DNA methylation acts through binding to specific proteins that could alter chromatin structure is discussed.

Animals↗
PubMed1989

Close linkage of the human cytochrome P450IIA and P450IIB gene subfamilies: implications for the assignment of substrate specificity.

We have isolated from human liver libraries two cytochrome P450 cDNA clones (lambda MP14 and lambda MP3) which are highly similar (83% over the coding region) to mouse testosterone 15 alpha hydroxylase and are therefore part of the cytochrome P450IIA gene subfamily. The P450IIA (CYP2A) gene subfamily was found to be closely linked to the P450IIB (CYP2B) subfamily and their chromosomal location could not be distinguished using somatic cell hybrids containing fragments of chromosome 19 between 19q12 and 19q13.2. Pulsed field gel electrophoresis indicates that both gene subfamilies are contained within 350-kb genomic DNA fragments, but were separated using various restriction enzymes. Northern blot analysis identified three P450IIA mRNAs each showing a wide inter-individual variation in their levels in the liver. High levels of P450IIA transcript were associated with high levels of P450IIB transcript suggesting that common factors may influence the expression of genes within these subfamilies. Genetic analysis has suggested previously that a member of the P450IIB subfamily is responsible for coumarin hydroxylase activity in the mouse. We discuss the possibility, based on our findings of tight linkage of the human P450IIA and IIB subfamilies, that a member of the IIA subfamily is a better candidate for this enzyme activity.

Amino Acid Sequence↗
PubMed1989

Human mononuclear cell function after 4 degrees C storage during 1-G and microgravity conditions of spaceflight.

Future space missions of long duration may require that autologous leukocytes be stored in flight for infusion to restore normal immune competence in crewmembers. Peripheral blood mononuclear cells (PBMNCs), as leukocyte concentrates in autologous plasma and 2% dextrose, were stored in the microgravity conditions provided by the U.S. Space Shuttle Columbia (Mission 61-C). Activity of PBMNC after space flight was compared with that from a series of preflight ground control experiments, which demonstrated in culture a progressive daily loss in mitogen-stimulated protein synthesis at 24 h and thymidine uptake at 72 h after storage for 7 d at 4 degrees C. Post-storage viabilities were at least 90% as determined by trypan dye exclusion. A progressive reduction in the percentage of PBMNC expressing cell-surface phenotype markers, which was similar for monocytes, B cells, and T-cell subsets, also occurred after storage. The ability of PBMNC, stored for 8 d in Columbia's middeck, to become activated and proliferate in vitro was similar to that of cells that remained in identical flight lockers on the ground as 1-G controls, thus indicating that PBMNCs were not adversely affected by storage under microgravity conditions.

Benzoates↗
PubMed1988

Operation Everest II: alterations in the immune system at high altitudes.

We investigated the effects on immune function after progressive hypobaric hypoxia simulating an ascent to 25,000 ft (7620 m) over 4 weeks. Multiple simultaneous in vitro and in vivo immunologic variables were obtained from subjects at sea level, 7500 ft (2286 m), and 25,000 ft during a decompression chamber exposure. Phytohemagglutinin-stimulated thymidine uptake and protein synthesis in mononuclear cells were reduced at extreme altitudes. Mononuclear-cell subset analysis by flow cytometry disclosed an increase in monocytes without changes in B cells or T-cell subsets. Plasma IgM and IgA but not IgG levels were increased at altitudes, whereas pokeweed mitogen-stimulated in vitro IgG, IgA, and IgM secretion was unchanged. During exposure to 25,000 ft, in vitro phytohemagglutinin-stimulated interferon production and natural killer-cell cytotoxicity did not change statistically, but larger intersubject differences occurred. IgA and lysozyme levels (nasal wash) and serum antibodies to nuclear antigens were not influenced by altitude exposure. These results suggest that T-cell activation is blunted during exposure to severe hypoxemia, whereas B-cell function and mucosal immunity are not. Although the mechanism of altered in vitro immune responsiveness after exposure to various environmental stressors has not been elucidated in humans, hypoxia may induce alterations in immune regulation as suggested by in vitro immune assays of effector-cell function.

Adult↗
PubMed1987

Human mononuclear cell in vitro activation in microgravity and post-spaceflight.

The results of postflight and inflight human in vitro lymphocyte experiments have been reviewed. The cumulative data indicate that mitogen-stimulated T-cell proliferation is blunted following short-duration missions. Since similar responses may also be obtained following exposure to non-spaceflight stressors (hypoxia and academic stress), it is unclear if microgravity per se aggravates this response. Our studies indicate that stress-induced impaired PHA- and PWM-stimulated activation can be detected within the first 24 hours in culture at the level of protein synthesis. While the mechanism for neuroendocrine-mediated blunted mitogen stimulated T cell proliferation has not been elucidated, it is not aggravated by autologous plasma and does not require changes in mononuclear cell subpopulations. While prior studies indicate lymphocyte activation is influenced by altering G forces on in vitro cultures, impaired cellular interactions or suboptimal microenvironments related to reduced cell densities in microgravity may contribute to the greatly impaired mitogen stimulated proliferation responses observed on Spacelab flights. It will be necessary to perform lymphocyte functional assays on crewmembers during spaceflight to determine to contribution of microgravity per se on altered human immune competence.

Female↗
PubMed1987

Gold pharmacokinetics in breast milk and serum of a lactating woman.

During 20 weeks of aurothioglucose therapy, gold in a mother's serum and breast milk and her nursing infant's serum and urine were measured. The mother's steady state plasma gold was 4.05 mg/l; it was 0.041 mg/l in breast milk. Only 0.0255 mg gold appeared in the breast milk/24 h. We calculated that only 0.1785 mg gold (0.71% of the weekly dose) would appear in the breast milk over a week. No gold (less than 5 X 10(-7) mg/l) was found in the infant's plasma or urine. It is very unlikely that more than minute amounts of gold are absorbed from the mother's breast milk when breast feeding an infant.

Adult↗
PubMedDate not supplied

Validity and reliability of the 'Ten Questions' questionnaire for detecting moderate to severe neurological impairment in children aged 6-9 years in rural Kenya.

BACKGROUND: The 'Ten Questions' Questionnaire (TQQ) is used to detect severe neurological impairment in children living in resource-poor countries. Its usefulness has been established in Asia and the Caribbean, but there are a few published studies from Africa. We evaluated the TQQ as part of a larger study of neurological impairment in a rural community, on the coast of Kenya. METHODS: The study was conducted in two phases from June 2001 to May 2002; in phase one, a community household screening of 10,218 children aged 6-9 years using the TQQ was performed. Phase two involved a comprehensive clinical and psychological assessment of all children testing positive on the TQQ (n = 810) and an equivalent number of those testing negative (n = 766). Data were interpreted using the impairment-specific approach. RESULTS: Overall, the sensitivity rates for screening the different impairments were: cognitive (70.0%), motor (71.4%), epilepsy (100%), hearing (87.4%) and visual (77.8%). All the specificity rates were greater than 96%. However, the positive predictive values were low, and ranged from 11 to 33%. CONCLUSIONS: These results are similar to those from other continents and provide evidence that the TQQ can be used to compare the epidemiology of moderate/severe impairment in different parts of the world. Furthermore, the TQQ can be used to screen for moderately/severely impaired children in resource-poor countries; however, the low positive predictive values mean that other assessments are required for confirmation.

Child↗
PubMedDate not supplied

Teaching infant CPR to mothers of cocaine-positive infants.

Cocaine abuse, a major problem in our society, has increased in women of childbearing age. Because cocaine-positive infants are at greater risk for apnea/sudden infant death syndrome (SIDS), their mothers need to be instructed in infant CPR. This study compared the use of a computerized interactive video learning system to the traditional infant CPR teaching method (lecture, video, and return demonstration) to determine the most effective method. This study indicated that mothers of cocaine-exposed infants can learn infant CPR in the immediate postpartum period and that the traditional method was found to be more effective. One unexpected positive outcome was the increase in these mothers' self-esteem.

Adult↗