Search PubMed⌕ Search

Biomedical subjects

M Skinner

Publications and source records attributed to M Skinner.

At least 37 records · Page 2Linked to original sources
PubMed2001

Improvements in circulating cholesterol, antioxidants, and homocysteine after dietary intervention in an Australian Aboriginal community.

BACKGROUND: Poor nutrition contributes to high rates of coronary heart disease among Australian Aboriginal populations. Since late 1993, the Aboriginal community described here has operated a healthy lifestyle program aimed at reducing the risk of chronic disease. OBJECTIVE: We evaluated the effectiveness of a community-directed intervention program to reduce coronary heart disease risk through dietary modification. DESIGN: Intervention processes included store management policy changes, health promotion activities, and nutrition education aimed at high-risk individuals. Dietary advice was focused on decreasing saturated fat and sugar intake and increasing fruit and vegetable intake. Evaluation of the program included conducting sequential, cross-sectional risk factor surveys at 2-y intervals; measuring fasting cholesterol, lipid-soluble antioxidants, and homocysteine concentrations; and assessing smoking status. Nutrient intakes were estimated from analysis of food turnover in the single community store. RESULTS: There was a significant reduction in the prevalence of hypercholesterolemia (age-adjusted prevalences were 31%, 21%, and 15% at baseline, 2 y, and 4 y, respectively; P < 0.001). There were significant increases in plasma concentrations of alpha-tocopherol, lutein and zeaxanthin, cryptoxanthin, and beta-carotene across the population. Retinol and lycopene concentrations did not change significantly. Mean plasma homocysteine concentrations decreased by 3 micromol/L. There was no significant change in smoking prevalence between the 2 follow-up surveys. There was an increase in the density of fresh fruit and vegetables and carotenoids in the food supply at the community store. CONCLUSION: This community-directed dietary intervention program reduced the prevalence of coronary heart disease risk factors related to diet.

Adolescent↗
PubMed2001

Variability in FMRP and early development in males with fragile X syndrome.

To test the hypothesis that variability in development in fragile X syndrome is related to FMRP (the protein deficient in this syndrome expression), we studied 53 males between 23 and 98 months of age. For the entire group, which included males with either mosaism, partially methylated full mutation, and fully methylated full mutation, FMRP expression ranged from 1% to 40% and accounted for a small but significant amount of variance in level, but not rate, of total development as well as motor, social, adaptive, cognitive, and language development. For males with a fully methylated full mutation, the association was in the hypothesized direction, but not statistically significant. Findings support the hypothesized relationship between FMRP and individual capabilities but suggest that other factors also play a major role.

Adolescent↗
PubMed2001

Role of religion in the lives of Latino families of young children with developmental delays.

We interviewed 250 parents of Mexican and Puerto Rican origin living in the United States who had young children with developmental delays to determine the role of religion in their lives. Quantitative results indicate that parents largely viewed themselves as religious, were affiliated with a formal religion, and participated in religious activities. Most parents viewed both church and faith as supportive, but faith was shown to provide more support. Repeated measures a analysis of variance found some intragroup variations in religious support and changes in support after learning of the child's condition. Thematic analysis revealed specific religious beliefs and practices parents viewed as supportive, and content and cultural models analyses indicated the religious frameworks by which parents interpreted their child's disability.

Adaptation, Psychological↗
PubMed2000

Congenital short colon with imperforate anus (pouch colon). Report of a case.

We report a case of a persistent cloaca and pseudoexstrophy associated with congenital pouch colon in a native-born American female child. This unusual anomaly occurs in two clinical settings. It has been reported in India as an isolated anomaly occurring primarily in males. Pouch colon also occurs in female patients with pseudoexstrophy or closed cloacal exstrophy. The typical anatomic features of this anomaly are discussed.

Abnormalities, Multiple↗
PubMed2000

Orthotopic liver transplantation for familial amyloidotic polyneuropathy: a pathological study.

Familial amyloidotic polyneuropathy (FAP), a hereditary form of systemic amyloidosis with clinically significant neuropathy and cardiomyopathy, is caused by a genetic defect of the transthyretin gene, which is mostly synthesized in the liver. Orthotopic liver transplantation (OLT) is thought to eliminate the amyloidogenic protein and currently is the only definitive treatment for this disorder. The aim of this study was to define the distribution and extent of amyloid deposition in tissues from these patients and evaluate the suitability of the resected FAP livers for transplantation into non-FAP patients. Surgical specimens from 14 patients removed at the time of OLT and autopsy tissues from 3 of the 14 were examined histologically using hematoxylin and eosin and Congo red-stained sections. The extent of amyloid deposits was evaluated, semiquantitatively graded from negative to marked, and correlated with clinical course and patient outcome. Amyloid deposits were consistently seen in hilar and vagus nerves. Liver lobular involvement was minimal in 1 and absent in the other 13 cases, with portal arterial amyloid deposits seen in 7 cases. At autopsy, extensive amyloid deposition in the heart was seen in all 3 cases with involvement of the conduction system. The extent of amyloid deposition at OLT did not correlate with the duration of symptoms before OLT or patient outcome after OLT. In conclusion, liver parenchymal involvement in FAP is minimal, and these explants are suitable for grafting in non-FAP patients. The recipients of such grafts must be carefully observed for the development of any amyloid-related disease, particularly cardiomyopathy. Of the tissues removed at OLT, the histopathologic confirmation of FAP is most consistently made by the examination of hilar and vagus nerves.

Adult↗
PubMed2000

Detection of transthyretin variants using immunoprecipitation and matrix-assisted laser desorption/ionization bioreactive probes: a clinical application of mass spectrometry.

In our continuing efforts to develop mass spectrometry-based methods for transthyretin (TTR) variant detection and characterization, we have sought to use matrix-assisted laser desorption/ionization (MALDI) bioreactive probes incorporating immobilized trypsin for screening purposes. These devices show good diagnostic potential as a clinical screening tool to detect amino acid substitutions in TTR. MALDI probes allow the on-probe generation of tryptic digests. The subsequent mass analysis of the on-probe digest yields the peptide map. The inherent advantages of this method include considerably reduced digestion times (minutes vs. hours), absence of autolysis products, minimized sample handling, and hence minimal sample loss. A further advantage is that the opportunity for loss of hydrophobic peptides is reduced because no sample transfer occurs. The method can be applied as a preliminary screen for TTR variants where TTR is isolated from patient serum through immunoprecipitation. This method should also be applicable to other proteins and suitable for automation.

Hemoglobins↗
PubMed2000

Early development, temperament, and functional impairment in autism and fragile X syndrome.

We compared the developmental status, functional abilities, and temperament of 31 young boys with fragile X syndrome (FXS) who did not have autism, matched on chronological age, gender, and race, with 31 boys with autism but no FXS. Children with autism exhibited a more variable profile of development in comparison with a relatively flat profile for children with FXS. Children with autism were significantly more delayed in social skills and were rated by observers as exhibiting a greater degree of impairment in cognitive, communication, and social skills. On temperament ratings, both groups were slower to adapt, less persistent, and more withdrawing than the reference group. Boys with FXS were rated as more active than the referent group, whereas boys with autism were rated as less intense, more distractible, having a higher threshold for response, and less rhythmic than the reference group. A smaller three-group analysis compared boys with FXS, boys with autism, and boys with both FXS and autism. Children with both autism and FXS were substantially more delayed than children with autism or FXS alone.

Age Factors↗
PubMed2000

Tracheobronchial amyloidosis. The Boston University experience from 1984 to 1999.

Tracheobronchial amyloidosis (TBA), an idiopathic disorder characterized by deposition of fibrillar proteins in the tracheobronchial tree, occurred in 10 patients referred to the Amyloid Program at Boston University over the past 15 years. Fewer than 100 cases of TBA have been described; only 1 series encompassed more than 3 patients. We analyzed our experience with biopsy-proven TBA to define better its natural history. Follow-up averaged approximately 8 years and was obtained in all cases, making this outcome reporting the largest and most complete to date. Three of these patients were prospectively studied for up to 24 months to examine the utility of bronchoscopy, computerized tomography (CT) imaging, and pulmonary function tests (PFTs) in monitoring disease progression. No patient with TBA developed signs or symptoms of systemic amyloidosis during the period reviewed. Conversely, tracheobronchial disease was not diagnosed in 685 patients with primary systemic (AL) amyloidosis during the 15-year study period at Boston University. Bronchoscopy proved most useful in establishing the diagnosis by biopsy. Narrowing of major airways limited its inspection of the tracheobronchial tree, however. In contrast, CT imaging provided quantitative assessment of airway narrowing and mural thickening--2 major consequences of amyloid infiltration. These CT features, in the presence of mural calcifications sparing the posterior tracheal membrane, have been reported in few disorders other than TBA. The ability of CT to map airway involvement and identify extraluminal manifestations of TBA made it the study of choice for establishing disease extent. Three patterns of disease were evident by CT imaging and bronchoscopic examination: proximal, mid, and distal airways involvement. Those with severe proximal disease had significantly decreased air flows, air trapping, and fixed upper airway obstruction on PFTs. Patients with distal disease had normal airflows. PFTs could not clearly distinguish proximal from severe mid airways disease. Thirty percent of patients died within 7-12 years after diagnosis, all having proximal or severe mid airways disease. Repeated rigid bronchoscopic debridement and laser treatments did not prevent progressive airways narrowing in patients dying from TBA. Most patients with mid airways involvement, and all distal airway cases, had either stagnant disease or slowly increasing amyloid deposits when followed for up to 14 years. In a small subset of patients followed prospectively, serial PFTs were most sensitive to disease progression. CT-derived measures of airway lumen diameter and wall thickness did not change significantly despite marked improvements in airflow after rigid bronchoscopy. Our experience suggests that serial PFTs and CT imaging together offer the best assessment of airway involvement and disease progression in patients with TBA. In the future, radiation therapy may provide more definitive treatment of TBA than debulking procedure have to date.

Adult↗
PubMed2000

Effectiveness of a community-directed 'healthy lifestyle' program in a remote Australian aboriginal community.

OBJECTIVE: To assess the sustainability and effectiveness of a community-directed program for primary and secondary prevention of obesity, diabetes and cardiovascular disease in an Aboriginal community in north-west Western Australia. METHOD: Evaluation of health outcomes (body mass index, glucose tolerance, and plasma insulin and triglyceride concentrations) in a cohort of high-risk individuals (n = 49, followed over two years) and cross-sectional community samples (n = 200 at baseline, 185 at two-year and 132 at four-year follow-ups), process (interventions and their implementation) and impact (diet and exercise behaviour). RESULTS: For the high-risk cohort, involvement in diet and/or exercise strategies was associated with protection from increases in plasma glucose and triglycerides seen in a comparison group; however, sustained weight loss was not achieved. At the community level, significant reductions were observed in fasting insulin concentration but no change in prevalence of diabetes, overweight or obesity. Weight gain remained a problem among younger people. Sustainable improvements were observed for dietary intake and level of physical activity. These changes were related to supportive policies implemented by the community council and store management. CONCLUSIONS: Community control and ownership enabled embedding and sustainability of program, in association with social environmental policy changes and long-term improvements in important risk factors for chronic disease. IMPLICATIONS: Developmental initiatives facilitating planning, implementation and ownership of interventions by community members and organisations can be a feasible and effective way to achieve sustainable improvements in health behaviours and selected health outcomes among Aboriginal people.

Adult↗
PubMed2000

Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome.

BACKGROUND AND AIMS: Post-dysenteric irritable bowel syndrome (PD-IBS) develops in up to 25% of patients following Campylobacter enteritis. Our aim was to define the pathological basis of this subgroup of IBS. METHODS: Twenty one patients (group 1) underwent serial rectal biopsy and gut permeability testing following acute Campylobacter enteritis as did 10 PD-IBS patients (group 2) and 12 asymptomatic controls. RESULTS: In group 1, enteroendocrine cell (EC) numbers were markedly increased initially and at six and 12 weeks (p<0.001) compared with controls. Gut permeability, as assessed by the lactulose/mannitol ratio, was significantly elevated, initially and at 12 weeks (p<0.005). CD3, CD4, and CD8 lymphocyte counts in the lamina propria and intraepithelial lymphocytes (IEL) were significantly increased initially compared with controls. At visit 1, EC numbers were positively correlated with CD3 counts (r=0.6, p=0.01). At one year, seven subjects (five with persistent loose stools) had rectal biopsies which showed significantly elevated EC, CD3, and IEL counts. In group 2, EC and IEL counts were significantly increased compared with controls (p<0.001), as was gut permeability (p<0.01). CONCLUSION: Increased EC, T lymphocytes, and gut permeability are acute changes following Campylobacter enteritis which can persist for more than a year and may contribute to PD-IBS.

Acute Disease↗
PubMed2000

Kaposi's sarcoma-associated herpesvirus gene sequences are detectable at low copy number in primary amyloidosis.

Primary amyloidosis (AL), like multiple myeloma (MM), results from a clonal proliferation of plasma cells. Recent detection of Kaposi's sarcoma-associated herpesvirus (KSHV) gene sequences in MM patients, although controversial, suggested that KSHV may also be present in AL. In the present study, we assayed for KSHV gene sequences in patients with primary AL independently in 2 laboratories. Nested polymerase chain reaction (PCR) was performed on DNA isolated from 21 bone marrow (BM) core biopsy samples to amplify orf26 and orf72, 2 regions of the KSHV genome. Eighteen of 21 (86%) BM core biopsy samples were KSHV PCR positive. BM aspirates from 16 of these 21 AL patients were cultured for 4-6 weeks to generate long term bone marrow stromal cells (LT-BMSCs), and 13 of 16 (81%) LT-BMSCs were also KSHV PCR positive. Results in all but 1 sample were consistent in the 2 laboratories. Sequencing of the PCR products in the 2 laboratories confirmed 94-98% and 95-98% homology to the published orf 26 and orf 72 KSHV gene sequences respectively, with interpatient base pair differences. Despite the presence of KSHV gene sequences, only 4/18 (22%) KSHV PCR positive patients demonstrated KSHV lytic antibodies by immunoblot assay. A sensitive assay performed on the BCBL-1 cell line confirmed the presence of KSHV at a very low copy number in AL. PCR using patient specific light chain gene primers also amplified DNA isolated from 2 AL BM core biopsies and 3 AL LT-BMSCs which were KSHV PCR positive, suggesting the presence of clonotypic cells. Our results therefore demonstrate KSHV gene sequences albeit at a very low copy number in the majority of BM core biopsies and LT-BMSCs from AL patients, and serological responses in only a minority of cases. Ongoing studies to identify viral transcripts and gene products will determine the biological relevance of KSHV in AL disease pathogenesis.

Adult↗
PubMed2000

Effects of alcohol on the response to hyperventilation of participants high and low in anxiety sensitivity.

BACKGROUND: Previous research suggests that high levels of anxiety sensitivity (AS; fear of anxiety symptoms) may constitute a risk factor for alcohol abuse. The present study evaluated the hypothesis that high AS levels may increase risk for alcohol abuse by promoting a heightened sober reactivity to theoretically relevant stressors and heightened sensitivity to alcohol's emotional reactivity dampening effects, which would negatively reinforce drinking in this population. METHODS: One hundred and two undergraduate participants (51 high AS, 51 low AS) with no history of panic disorder were assigned to either a placebo, low-dose alcohol, or high-dose alcohol beverage condition (17 high AS, 17 low AS per beverage condition). After beverage consumption and absorption, participants underwent a 3 min voluntary hyperventilation challenge. RESULTS AND CONCLUSIONS: High-AS/placebo participants displayed greater affective and cognitive reactivity to the challenge than low-AS/placebo participants, which indicated increased fear and negative thoughts (e.g., "losing control") during hyperventilation among sober high AS individuals. Dose-dependent alcohol dampening of affective and cognitive reactivity to hyperventilation was observed only among high-AS participants, which suggested that high-AS individuals may be particularly sensitive to alcohol-induced reductions in their degree of fear and negative thinking in response to the experience of physical arousal sensations. In contrast, dose-dependent alcohol dampening of self-reported somatic reactivity was observed among both high- and low-AS participants. We discuss implications of these results for understanding risk for alcohol abuse in high-AS individuals, as well as directions for future research.

Adult↗
PubMed2000

A re-evaluation of localized hypoplasia of the primary canine as a marker of craniofacial osteopenia in European Upper Paleolithic infants.

Localized hypoplasia of the primary canine (LHPC) occurs in prehistoric and contemporary populations with prevalence varying from 0 to 89%. One of the highest prevalences ever reported is Upper Paleolithic infants from Europe where 70% are affected. In that LHPC is found in relatively high proportions of contemporary children with reported or suspected malnutrition, it is important to investigate the etiology of LHPC. Previous research indicates that LHPC occurs in two steps: craniofacial osteopenia results in temporary fenestration of the cortical bone overlying the primary canine crypt; secondly, minor physical trauma to the perioral region impacts on the unprotected forming tooth crown resulting in a small pit visible on the labial surface of the erupted tooth. Investigation of the prenatal diet of mothers whose children are shown later to have LHPC found mothers are significantly low in vitamin A. Hitherto an animal model for this problem has been lacking. Recently Newell and Skinner have recognized that LHPC occurs very commonly in orangutans. Recent study of infant jaws from Pongo pygmaeus (n=75) and Pan paniscus (n=39) shows all stages of fenestration and healing of the labial bone of the primary canine crypt. 85% of orangutan and 62% of bonobos show LHPC. Current research is directed at bioavailability of vitamin A to ape infants. LHPC is a marker of malnutrition; a common factor that could link orangutan and Upper Paleolithic mothers is low dietary fat intake. A minimal level of dietary fat is required for gut absorption of both vitamin A and carotenoids.

Animals↗
PubMed1999

Identification of a novel substitution in the constant region of a gene coding for an amyloidogenic kappa1 light chain.

Current concepts regarding the association between immunoglobulin (Ig) light chain structure and AL amyloidosis (AL) emphasize Ig variable region amino acid substitutions because the majority of light chain amyloid fibrils that have been sequenced contain amino termini of the variable region with only small amounts of the constant region. In this report, we describe a patient with rapidly progressive AL whose amyloid deposits contained primarily monoclonal kappa light chain constant region fragments. We sequenced and analyzed this AL protein, determining that it was an O18-O8 kappa1 variant and that the constant region possessed an unusual Ser-->Asn substitution at position 177. Using pre-mortem bone marrow cells, we cloned and sequenced the cDNA for this AL protein (HCAK1) and, using DNA from post-mortem somatic tissue, we cloned and sequenced the patient's kappa germline O18-O8 donor and kappa constant region (Ckappa) gene segments. The cDNA that coded for HCAK1 contained a variable region that was derived from O18-O8, showing 96.1% homology to germline, and a Ckappa that had a nucleotide substitution (AGC to AAC), resulting in the 177Ser-->Asn replacement. Two Ckappa genes were cloned from somatic tissue DNA, one identical to a known Ckappa sequence and another containing this substitution which likely is a new Ckappa allotype. Our findings indicate that further investigation is warranted into the contributions genetic polymorphisms and light chain constant regions may make to amyloidogenesis.

Amino Acid Sequence↗