Biomedical subjects

M L Hughes

Publications and source records attributed to M L Hughes.

At least 19 recordsLinked to original sources

PubMed2001

Evidence for a susceptibility locus on chromosome 6q influencing phonological coding dyslexia.

A linkage study of 96 dyslexia families containing at least two affected siblings (totaling 877 individuals) has found evidence for a dyslexia susceptibility gene on chromosome 6q11.2-q12 (assigned the name DYX4). Using a qualitative phonological coding dyslexia (PCD) phenotype (affected, unaffected, or uncertain diagnoses), two-point parametric analyses found highly suggestive evidence for linkage between PCD and markers D6S254, D6S965, D6S280, and D6S251 (LOD(max) scores = 2.4 to 2.8) across an 11 cM region. Multipoint parametric analysis supported linkage of PCD to this region (peak HLOD = 1.6), as did multipoint nonparametric linkage analysis (P = 0.012). Quantitative trait linkage analyses of four reading measures (phonological awareness, phonological coding, spelling, and rapid automatized naming speed) also provided evidence for a dyslexia susceptibility locus on chromosome 6q. Using a variance-component approach, analysis of phonological coding and spelling measures resulted in peak LOD scores at D6S965 of 2.1 and 3.3, respectively, under 2 degrees of freedom. Furthermore, multipoint nonparametric quantitative trait sibpair analyses suggested linkage between the 6q region and phonological awareness, phonological coding, and spelling (P = 0.018, 0.017, 0.0005, respectively, for unweighted sibpairs < 18 years of age). Although conventional significance thresholds were not reached in the linkage analyses, the chromosome 6q11.2-q12 region clearly warrants investigation in other dyslexia family samples to attempt replication and confirmation of a dyslexia susceptibility gene in this region.

Adolescent↗

PubMed2001

Molecular quantification of human beta-glucuronidase levels in a patient with Vohwinkel's syndrome.

The skin must undergo the process of keratinization in order to perform its functions. During the process of differentiation, certain genes are activated while others are repressed, leading to changes in structural proteins and enzymes and in the synthesis of various lipids. An error in any of these steps can ultimately impair the process of keratinization. Vohwinkel's syndrome is the direct result of a defect in keratinization. Patients who have this epidermolytic palmoplantar keratoderma present clinically with hyperkeratosis of the stratum corneum. Hyperkeratosis has been linked to an increase in beta-glucuronidase levels. The authors studied the absolute concentration of human beta-glucuronidase in a patient with Vohwinkel's syndrome as determined through a double-antibody sandwich enzyme-linked immunosorbent assay and a Western blot assay of the blood, urine, and skin of the patient.

Adult↗

PubMed2000

Postprandial decrease in splenic volume demonstrated by magnetic resonance imaging and stereology.

The aim of this study was to determine if the volume of the spleen changes after food intake. We applied an unbiased and efficient method for splenic volume estimation using magnetic resonance imaging (MRI) in combination with modern design stereology. MR images of the spleen were obtained for 10 healthy volunteers (five men and five women; mean age 28.9 years [range 23-35 years]) without a history of splenomegaly. The initial scans were performed in the morning after overnight fasting. Each volunteer then consumed a standard balanced meal weighing 500 g [2,460 kJ (627 kcal) energy] with 500 ml of still mineral water. Second identical MR scans were performed approximately 1 hr later. Postprandially, splenic volume decreased by an average of 6.6% (P = 0.005), probably due to increased splanchnic blood flow after food intake.

Adult↗

PubMed2000

Pulmonary vascular resistance and reactivity in children with end-stage cardiomyopathy.

Pulmonary vascular resistance (PVR) and reactivity were compared in 63 children with end-stage cardiomyopathy (CM) referred for cardiac transplantation. Diagnostic category of CM was the sole determinant of PVR. Compared with other patients, children with restrictive CM were younger at diagnosis and had a significantly higher pulmonary vascular resistance index (PVRI). Children with a baseline PVRI of up to 11.8 units per meter squared (U.m(2)) who showed reactivity underwent successful orthotopic cardiac transplantation.

Adolescent↗

PubMed2000

Obesity in women from developing countries.

OBJECTIVES: The key objective was to estimate obesity (>/=30 kg/m2) in women 15-49 y from developing countries. A second objective was to study how obesity varies by educational level and by residence in urban and rural areas. A third objective was to investigate how national incomes shape the relationship between obesity and eduction or residence. DESIGN: The analyses use cross-sectional data from nationally representative surveys from developing countries carried out in the last decade. Most of the surveys were Demographic Health Surveys (DHS). Data from a survey from the USA are used for comparison. SETTING: The 39 surveys used come from 38 developing countries and the USA. SUBJECTS: A total of 147,938 non-pregnant women 15-49 y were included in the analyses. RESULTS: The percentage of obese women was 0.1% in South Asia, 2.5% in Sub-Saharan Africa, 9. 6% in Latin America and the Caribbean, 15.4% in Central Eastern Europe/Commonwealth of Independent States (CEE/CIS), 17.2% in the Middle East and North Africa, and 20.7% in the USA. Levels of obesity in countries increased sharply until a gross national product of US$1500 per capita (1992 values) was reached and changed little thereafter. In very poor countries, such as in Sub-Saharan Africa, obesity levels were greatly concentrated among urban and higher educated women. In more developed countries, such as those in Latin America and the CEE/CIS regions, obesity levels were more equally distributed in the general population. CONCLUSIONS: Based on the analyses presented and on a review of the literature, it is concluded that obesity among women is a serious problem in Latin America and the Caribbean, the Middle East and North Africa, and the CEE/CIS region. Obesity is less of a concern in Sub-Saharan Africa, China and South Asia. Obesity levels increased over time in most of the limited number of countries with data, but at varying rates. Rising national incomes in developing countries and increased 'Westernization' will most likely lead to increased levels of obesity in the future. SPONSORSHIP: Financial support was provided by the Food and Nutrition Program of the Pan American Health Organization and by the World Bank.

Adolescent↗

PubMed2000

Overweight and obesity in preschool children from developing countries.

OBJECTIVES: To estimate levels and trends in overweight and obesity in preschool children from developing countries; to study how overweight varies by the educational level of the mother, by urban or rural residence, and by gender; to investigate how these relationships are related to the gross national product (GNP). DESIGN: 71 national nutrition surveys since 1986 from 50 countries were used. SUBJECTS: 150,482 children 12 to 60 months from the most recent survey from each country were the primary sample. MEASUREMENTS: Overweight and obesity were defined as weight-for-height (>1 or >2 s.d., respectively) of the WHO/NCHS reference curves. Stunting was <-2 s.d. of the same reference. Urban was as defined in each of the surveys and higher education was defined as at least one year of secondary schooling or higher. RESULTS: 32 of 50 countries had a prevalence of obesity below 2.3%, the value in the reference population. The prevalences of overweight and obesity were lowest in Asia and in Sub-Saharan Africa. In 17 countries with serial data, no consistent regional trends could be detected. Overweight was more common in urban areas, in children of mothers with higher education, and in girls; these relationships did not differ by GNP but GNP was related negatively to stunting and positively to overweight. CONCLUSIONS: Obesity does not appear to be a public health problem among preschool children in Asia and Sub-Saharan Africa. In a number of countries in Latin America and the Caribbean, the Middle East and North Africa, and the region of Central Eastern Europe/Commonwealth of Independent States, levels are as high as in the United States.

Child Welfare↗

PubMed2000

The relationship between EAP and EABR thresholds and levels used to program the nucleus 24 speech processor: data from adults.

OBJECTIVE: The objective of this study was to determine the relationship between electrically evoked whole nerve action potential (EAP) and electrical auditory brain stem response (EABR) thresholds and MAP threshold (T-level) and maximum comfort level (C-level) for subjects who use the Nucleus 24 cochlear implant system. DESIGN: Forty-four adult Nucleus 24 cochlear implant users participated in this study. EAP thresholds were recorded using the Neural Response Telemetry System developed by Cochlear Corporation. EABR thresholds were measured for a subset of 14 subjects using standard evoked potential techniques. These physiologic thresholds were collected on a set of five electrodes spaced across the cochlea, and were then compared with behavioral measures of T-level and C-level used to program the speech processor. RESULTS: EAP thresholds were correlated with MAP T- and C-levels; however, the correlation was not strong. A technique for improving the correlation by combining measures of T- and C-levels made on one electrode with the EAP thresholds was presented. Correlations between predicted and measured T- and C-levels using this technique were 0.83 and 0.77, respectively. Similar results were obtained using the EABR thresholds for a smaller set of subjects. In general, EABR thresholds were recorded at levels that were approximately 4.7 programming units lower than EAP thresholds. CONCLUSIONS: Either EAP or EABR thresholds can be used in combination with a limited amount of behavioral information to predict MAP T- and C-levels with reasonable accuracy.

Acoustic Stimulation↗

PubMed2000

Comparison of EAP thresholds with MAP levels in the nucleus 24 cochlear implant: data from children.

OBJECTIVE: The purpose of this study is to examine the relationship between the electrically evoked compound action potential (EAP) thresholds and the MAP thresholds (T-levels) and maximum comfort levels (C-levels) in children implanted with the Nucleus 24 device. DESIGN: EAP thresholds were measured using the Neural Response Telemetry system of the Nucleus 24 device. Twenty children implanted with the Nucleus 24 cochlear implant participated in this study. EAP thresholds were compared with the behavioral measures of T- and C-level used to construct the MAP these children used on a daily basis. For these subjects, both EAP and MAP T- and C-levels were obtained the same visit, which occurred at 3 to 5 mo postconnection. RESULTS: EAP thresholds were shown to fall between MAP T- and C-level for 18 of 20 subjects tested; however, considerable variability across subjects was noted. On average, EAP thresholds fell at 53% of the MAP dynamic range. Correlations between EAP threshold and MAP T- and C-level improved substantially when combined with behavioral measures obtained from one electrode in the array. CONCLUSIONS: Moderate correlations were found between EAP thresholds and MAP T- and C-levels for the children participating in this study. However, a technique is described for improving the accuracy of predictions of MAP T- and C-levels based on EAP data combined with a small amount of behavioral information.

Acoustic Stimulation↗

PubMed2000

Electrically evoked compound action potentials recorded from subjects who use the nucleus CI24M device.

The ability to directly measure the response to a pulse with the NRT opens the possibility of using this system to characterize the responses to more complex stimuli. An example is the responses to constant-amplitude pulse trains. With further changes in the software that controls the implant, it may be possible to characterize the responses to modulated pulse trains or other stimuli that better approximate the type of stimuli that are normally used with a cochlear implant speech processor.

Action Potentials↗

PubMed1999

Summary of results using the nucleus CI24M implant to record the electrically evoked compound action potential.

OBJECTIVE: This study outlines a series of experiments using the neural response telemetry (NRT) system of the Nucleus CI24M cochlear implant to measure the electrically evoked compound action potential (EAP). The goal of this investigation was to develop a protocol that allows successful recording of the EAP in a majority of CI24M cochlear implant users. DESIGN: Twenty-six postlingually deafened adults participated in this study. A series of experiments were conducted that allowed us to examine how manipulation of stimulation and recording parameters may affect the morphology of the EAP recorded using the Nucleus NRT system. RESULTS: Results of this study show consistent responses on at least some electrodes from all subjects. Cross-subject and cross electrode variations in both the growth of the response and the temporal refractory properties of the response were observed. The range of stimulus and recording parameters that can be used to record the EAP with the Nucleus NRT system is described. CONCLUSIONS: Using the protocol outlined in this study, it is possible to reliably record EAP responses from most subjects and for most electrodes in Nucleus CI24M cochlear implant users. These responses are robust and recording these responses does not require that the subject sleep or remain still. Based on these results, a specific protocol is proposed for measurement of the EAP using the NRT system of the CI24M cochlear implant. Potential clinical implications of these results are discussed.

Adult↗

PubMed1999

Relationship between EABR thresholds and levels used to program the CLARION speech processor.

The purpose of this study was 1) to describe the relationship between electrically evoked auditory brain stem response (EABR) thresholds and the behavioral measures needed to program the speech processor of the CLARION Multi-Strategy Cochlear Implant, and 2) to determine whether the relationship between EABR threshold and the behavioral levels used to program the Clarion device was correlated with the temporal integration abilities of these subjects. The EABR thresholds, psychophysical thresholds, and the Clarion speech processor programming levels were recorded from 29 postlingually deafened adults. The mean EABR thresholds approximated most comfortable levels (M levels) for the programming stimulus. However, intrasubject variability was substantial. Significant intrasubject variability in temporal integration also was observed. Correlations were found between the ability of a cochlear implant user to perform temporal integration and the relationship between his or her EABR threshold and the threshold for the programming stimulus.

Adult↗

PubMed1999

Persistent hypophyseal (craniopharyngeal) canal.

Two cases with a broad persistent hypophyseal canal connecting pituitary fossa and nasopharynx are presented. Both had nasopharyngeal surgery in early childhood and presented later with hypopituitarism. Coronal CT demonstrated the defects with no visible pituitary tissue. The spectrum of basal skull defects is discussed. Children with midline nasal polyps should have CT or MRI of the skull base prior to surgery to prevent inadvertent hypophysectomy.

Adult↗

PubMed1998

Role of chest CT scanning in the management of patients presenting with head and neck cancer.

BACKGROUND: The detection of synchronous tumors, whether they be second primaries or distant metastases, in patients with head and neck carcinoma drastically affects prognosis and may alter management. Computerized tomographic (CT) scanning of the chest is an effective screening investigation in this group of patients, both in the detection of synchronous second primary tumors, the incidence of which in this study is 15%, and for accurate staging of metastatic pulmonary disease. The incidence of synchronous tumors in patients who are initially seen with head and neck squamous cell carcinoma (HNSCC) has been reported in large retrospective studies as being between 1% and 3%. These may be either second primary tumors or metastases, and the lung is the commonest site for both. METHODS: Eighty-one head and neck cancer patients (67 primary and 14 secondary referrals) treated at the Royal Liverpool University Hospital between 1994 and 1996 underwent CT scanning of the chest with ultrasound of the liver as part of their routine staging. The results were compared with standard chest x-rays also performed in each patient. RESULTS: Fourteen patients had pulmonary tumors detected on the chest CT scan. In 67 patients, the scan was negative. Patients with negative scans tended not to have neck node metastases (64%), whereas patients with positive scans were much more likely to have neck node metastases with negative necks present in only 36% of patients. Where multivariate analysis was carried out, there was a correlation between neck node metastases and positive CT scans of the chest (estimate = 0.5755, standard error = 0.3066, chi2(1) = 6.73, p .047). The sensitivity of chest x-ray compared with CT scan was only 21 % and the specificity 99%. The positive predictive value of a chest x-ray was 75% and the negative predictive value 86%. Intra-abdominal lesions were detected in two patients, one in the liver and one in the adrenal gland. In the latter patient, this was an isolated lesion, but in the former, the chest scan was also positive. In the 67 patients, who were initially seen at the Royal Liverpool Hospital (primary referrals), the incidence of synchronous tumors was 15%. CONCLUSIONS: Synchronous tumors, whether they be second primary tumors or distant metastases, are more common in patients initially seen with head and neck cancer than is realized, their incidence being significantly higher in those patients with cervical metastases. Computerized tomographic scanning of the chest is a more effective screening investigation than chest x-ray in this group of patients and is now used routinely in our department prior to undertaking major head and neck surgery.

Adult↗

PubMed1998

Obesity in Latin American women and children.

National surveys conducted since 1982 were used to assess maternal and child obesity in Latin American and Caribbean countries and in U. S. residents of Mexican descent. Obesity in women, a body mass index (BMI) >/=30 kg/m2, was 3% in Haiti, 8-10% in eight Latin American countries and 29% in Mexican Americans. Median BMI for Latin American women were near or above the 50th percentile of the general U.S. population; values exceeded the 75th percentile in the case of Mexican Americans. The prevalence of overweight (>1 SD above mean weight-for-height) in children 1-5 y of age ranged from 6% in Haiti to 24% in Peru among 13 countries. Overweight occurred in 24% of Mexican-American children. Prevalences of overweight in children and of obesity in women were greater in urban areas and in households of higher socioeconomic status. Overweight in children increased with higher maternal education; however, in some countries, obesity in women decreased with higher education. No general pattern of change over time was observed in eight countries in overweight in children. Obesity in women increased in the three countries with such data and in Mexican-American women and children. There was a tendency for greater national incomes to be associated with greater obesity levels in women and with lower levels of stunting in children. Levels of obesity in the region indicate a public health concern, particularly among women, considering that studies have identified mortality and morbidity risks associated with obesity in adults.

Adult↗

PubMed1997

Abdominal wall endometriosis after amniocentesis. A case report.

BACKGROUND: Amniocentesis is a procedure performed commonly in the evaluation and early diagnosis of fetal chromosomal abnormalities. The procedure is safe, with a major complication rate of 0.5% and the most common minor complication, spotting. CASE: A 27-year-old woman underwent amniocenteses to document pulmonary maturity prior to cesarean section. She presented 18 months later with a 6-month history of left abdominal wall pain and a mass that enlarged 2 days prior to menses and shrank 1 week after. The mass was located at the prior amniocentesis site. Excisional biopsy revealed endometriosis on final pathology. CONCLUSION: To our knowledge, this is the first well-documented case of abdominal wall endometriosis following third-trimester amniocentesis. The procedure should be considered a possible complication of amniocentesis.

Abdominal Muscles↗

PubMed1995

Heparan sulfate stimulates extracellular matrix protein synthesis by mesangial cells in culture.

Heparan sulfate, a glycosaminoglycan which is a component of the glomerular basement membrane and the mesangial matrix, has been demonstrated to inhibit mesangial cell growth. The present studies investigated the effects of heparan sulfate on extracellular matrix protein synthesis by cultured rat mesangial cells. Mesangial cells were metabolically labeled with 35S-methionine and specific extracellular matrix proteins were immunoprecipitated from supernatant and cellular fractions. The following extracellular proteins were assayed: type I collagen, type IV collagen, type V collagen, laminin and fibronectin. Western blotting was performed to demonstrate the specificity of the immunoprecipitates. Heparan sulfate decreased cell number by 23.5%, p < 0.05, while chondroitin sulfate, another glycosaminoglycan, increased cell number by 11.5%, p < 0.05. Heparan sulfate significantly increased type V collagen and laminin in the cellular material and significantly increased laminin and fibronectin in the supernatant material. Chondroitin sulfate had no effect on matrix protein synthesis. Thus, heparan sulfate has effects on both mesangial cell growth and synthesis of matrix proteins and alterations in heparan sulfate may play a role in the development of glomerulosclerosis.

Animals↗

PubMed1995

Insulin-like growth factor-1 stimulates production of mesangial cell matrix components.

Diabetic nephropathy is characterized by mesangial cell proliferation and expansion of the mesangial matrix. Insulin-like growth factor-1 (IGF-1) increases in the kidney early in experimental diabetes. The effect of IGF-1 on mesangial cell proliferation and synthesis of extracellular matrix (ECM) proteins was examined to test the hypothesis that IGF-1 stimulates mesangial cells to synthesize ECM proteins. ECM proteins were measured by immunoprecipitation after metabolic labeling of rat mesangial cells in culture. IGF-1 caused a 2.4-fold increase in mesangial cell proliferation as measured by 3H-thymidine incorporation. IGF-1 caused an increase in cellular laminin, fibronectin and type IV collagen, 46.8 +/- 15.4%, 31.3 +/- 11.4%, and 27.7 +/- 12.6% increase respectively compared to control cells. IGF-1 did not effect cellular type 1 collagen, decrease of 8.2 +/- 8.7%. There was a trend toward increased total protein synthesis by IGF-1, 36.5 +/- 2.5%. In summary, IGF-1 stimulates ECM component production by mesangial cells. Thus, IGF-1 has the capacity to mediate the histologic changes characteristic of diabetic nephropathy.

Animals↗

PubMed1994

(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl) isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: I. In vitro characterization.

A diversity of nicotinic acetylcholine receptor (nAChR) subtypes has been identified in mammalian brain using recombinant DNA technology. Alterations in the activity of these acetylcholinegated ion channels have been implicated in a number of central nervous system disorders including Alzheimer's disease (AD). The potential therapeutic usefulness of (-)-nicotine [(S)-3-(1-methyl-2-pyrrolidinyl) pyridine], the prototypic agonist at nAChRs, is severely limited by side effects that are the result of activation of both cholinergic and noncholinergic pathways in the central and peripheral nervous systems. This study sought to determine the in vitro selectivity of (S)-3-methyl-5-(1methyl-2-pyrrolidinyl)isoxazole (ABT 418), a novel analog of (-)-nicotine in which the pyridine ring was replaced with an isoxazole bioisotere, to activate nAChRs. ABT 418 was a potent inhibitor of [3H]-cytisine binding to nAChR in rat brain (Ki = 3 nM) but was inactive (Ki > 10,000 nM) in 37 other receptor/neurotransmitter-uptake/enzyme/transduction system binding assays, including those for alpha-bungarotoxin, muscarinic and 5-hydroxytryptamine3 receptors. In PC12 cells, patch-clamp studies indicated that ABT 418 was an agonist with an EC50 value of 209 microM, a potency to activate cholinergic channel currents some 4-fold less than that of (-)-nicotine (52 microM). Channel current responses elicited by ABT 418 were prevented by the cholinergic channel blocker, mecamylamine. ABT 418 was also approximately 10-fold less potent (EC50 value = 380 nM) than (-)-nicotine (40 nM) in increasing [3H]-dopamine release from rat striatal slices, an effect that was blocked by the nAChR antagonist, dihydro-beta-erythroidine (10 microM).2+ In contrast, ABT 418 appeared equipotent with (-)-nicotine in enhancing 86Rb+ flux from mouse thalamic synaptosomes. ABT 418 demonstrated an in vitro pharmacological profile of cholinergic channel activation that was robust at some nAChR, but not others. The reasons for this are unclear. However, a nAChR subtype selectivity may account for the in vitro potency differences of ABT 418 on various neurotransmitter systems, and the substantial separation between the cognitive enhancement/anxiolytic benefits, and the reduced central nervous system side-effect liabilities seen in vivo. ABT 418 represents the first neuronal nAChR ligand that differentiates the toxicities/liabilities and other negative aspects normally associated with liabilities and other negative aspects normally associated with (-)-nicotine from the potential pharmacological benefits of selective cholinergic channel activation.

Alkaloids↗