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Biomedical subjects

M E Wilson

Publications and source records attributed to M E Wilson.

At least 91 records · Page 5Linked to original sources
PubMed2000

Using treatment failure under effective directly observed short-course chemotherapy programs to identify patients with multidrug-resistant tuberculosis.

SETTING: Public ambulatory care centers in three districts of northern metropolitan Lima, Peru. OBJECTIVE: To document drug resistance patterns of isolates of Mycobacterium tuberculosis from patients identified as treatment failures under a model tuberculosis (TB) control program based on directly observed, short-course chemotherapy (DOT-SCC). DESIGN: Case series. RESULTS: In a referred, consecutive sample of 173 patients identified as treatment failures on DOT-SCC, 160 (92.5%) had culture-positive TB. Of those 160, 150 (93.8%) had active, pulmonary multidrug-resistant TB (MDR-TB, resistance to at least isoniazid [INH] and rifampicin [RIF]). Sixty of the 150 (40.0%) had isolates resistant to at least INH, RIF, ethambutol (EMB) and pyrazinamide (PZA), the initial first-line empiric treatment regimen used locally. Forty-four (29.3%) had isolates resistant to at least INH, RIF, EMB, PZA and streptomycin (SM), the first retreatment regimen. This series of patients had isolates resistant to a mean of 4.5 of the ten drugs tested. The local profile of multidrug resistance is very different from that obtained from national data from Peru. CONCLUSION: In this setting, treatment failure on DOT-SCC is strongly predictive of active MDR-TB. Because of existing local drug resistance patterns in northern Lima, 89.3% of MDR-TB patients identified as treatment failures will receive ineffective therapy with two or fewer secondary TB drugs if they are given the five-drug empiric retreatment regimen endorsed by the World Health Organization. Further short-course chemotherapy for these patients would only serve to amplify ominous existing drug resistance patterns.

Antitubercular Agents↗
PubMed2000

Bilateral idiopathic Brown's syndrome with delayed onset in the second eye.

PURPOSE: We describe 6 cases of a previously unreported variation of bilateral Brown's syndrome that presented in congenital form in one eye and developed later in the fellow eye with no underlying cause. METHODS: We reviewed the clinical records of 6 patients from 6 separate practices to determine whether there were any common clinical features on presentation or in their clinical courses. RESULTS: All 6 patients were diagnosed with unilateral congenital Brown's syndrome at the first ophthalmologic assessment but showed no evidence of the syndrome in the fellow eye. In 5 cases the contralateral syndrome developed in the second eye after surgery was performed on the first eye, and in 1 case it developed before any surgery was done. The ages at onset of the syndrome in the second eye ranged from 2 to 8 years. None of the children had any evidence of systemic illness or local orbital disease to explain an acquired Brown's syndrome. CONCLUSION: To our knowledge, this is the first reported series of cases of bilateral Brown's syndrome that manifested sequentially in the eyes with no known causes for an acquired syndrome in the second eye. This finding supports the premise that congenital and acquired Brown's syndrome are on a continuum with a common pathophysiology of restriction of free movement of the superior oblique tendon in the trochlea.

Child↗
PubMed1999

Estradiol modulates bcl-2 in cerebral ischemia: a potential role for estrogen receptors.

We have shown that physiological levels of estradiol exert profound protective effects on the cerebral cortex in ischemia induced by permanent middle cerebral artery occlusion. The major goal of this study was to begin to elucidate potential mechanisms of estradiol action in injury. Bcl-2 is a proto-oncogene that promotes cell survival in a variety of tissues including the brain. Because estradiol is known to promote cell survival via Bcl-2 in non-neural tissues, we tested the hypothesis that estradiol decreases cell death by influencing bcl-2 expression in ischemic brain injury. Furthermore, because estradiol may protect the brain through estrogen receptor-mediated mechanisms, we examined expression of both receptor subtypes ERalpha and ERbeta in the normal and injured brain. We analyzed gene expression by RT-PCR in microdissected regions of the cerebral cortex obtained from injured and sham female rats treated with estradiol or oil. We found that estradiol prevented the injury-induced downregulation of bcl-2 expression. This effect was specific to bcl-2, as expression of other members of the bcl-2 family (bax, bcl-x(L), bcl-x(S), and bad) was unaffected by estradiol treatment. We also found that estrogen receptors were differentially modulated in injury, with ERbeta expression paralleling bcl-2 expression. Finally, we provide the first evidence of functional ERbeta protein that is capable of binding ligand within the region of the cortex where estradiol-mediated neuroprotection was observed in cerebral ischemia. These findings indicate that estradiol modulates the expression of bcl-2 in ischemic injury. Furthermore, our data suggest that estrogen receptors may be involved in hormone-mediated neuroprotection.

Animals↗
PubMed1999

Induction of specific cell-mediated immunity in mice by oral immunization with Salmonella expressing Onchocerca volvulus glutathione S-transferase.

Cellular and humoral immune responses of mice to Onchocerca volvulus glutathione S-transferase (OvGST) presented via in vivo expression in attenuated Salmonella typhimurium were examined and compared with the same antigen administered by subcutaneous injection with Freund's adjuvant. After infection with recombinant S. typhimurium, maximal numbers of bacteria were recovered from the mesenteric lymph nodes and spleens during the second week postinfection. By weeks 3-4, bacteria were absent from these tissues. Splenocytes from mice infected with S. typhimurium expressing OvGST showed significant and specific proliferative responses to OvGST, whereas the non-recombinant S. typhimurium controls and those which received the antigen by subcutaneous injection with Freund's adjuvant did not. Mice infected with recombinant S. typhimurium had elevated IFN-gamma levels over non-recombinant S. typhimurium and placebo controls. but IL-4 and IL-5 levels were low and did not differ significantly between these groups. Antibody responses to OvGST antigen expressed by a recombinant Salmonella vaccine or delivered in a purified form with Freund's adjuvant were moderate to high. These data suggest that Salmonella can be used as a vaccine delivery vector that induces specific cellular and humoral immune responses to Onchocerca volvulus antigens. This is the first report to describe the successful application of a filarial antigen in a live-vector delivery system as well as the first recombinant based filarial vaccine to elicit a cellular immune response similar to that described for putative immune endemics.

Administration, Oral↗
PubMed1999

Elastic properties and scanning electron microscopic appearance of manual continuous curvilinear capsulorhexis and vitrectorhexis in an animal model of pediatric cataract.

PURPOSE: To compare the tear resistance of anterior capsulotomies using manual continuous curvilinear capsulorhexis (CCC) and vitrector-cut capsulotomy (vitrectorhexis) techniques in an animal model of the pediatric eye and in 2 pairs of human infant eyes. SETTING: Department of Ophthalmology, Storm Eye Institute, Medical University of South Carolina, Charleston, South Carolina, USA. METHODS: Continuous curvilinear capsulorhexis and automated vitrectorhexis capsulotomy techniques were performed in 20 pig eyes, 10 with each technique. The capsules were then stretched until they ruptured. The forces required for rupture after each technique were compared. The forces required for rupture of the pig eye lens capsule were also compared with those required for the human infant eye lens capsule. Scanning electron microscopy was performed in each group following intraocular lens (IOL) insertion. RESULTS: All capsules stretched adequately for IOL insertion. The percentage of stretch prior to rupture was higher in the capsulorhexis group (mean 157%, range 147% to 169%) than in the vitrectorhexis group (mean 135%, range 124% to 147%) (P < .001). The percentage of stretch in the human infant eyes was not statistically different from that in the porcine eyes (P > .05). CONCLUSIONS: The manual CCC offered greater resistance to capsule tearing than the vitrectorhexis and also revealed a more smooth, regular edge. It therefore remains the gold standard. However, the vitrectorhexis displayed more than adequate resistance to unwanted anterior capsule tears when used for IOL insertion through capsulotomy sizes currently used in clinical practice.

Animals↗
PubMed1999

Unilateral intraocular lens implantation during the first six months of life.

PURPOSE: The purpose of this study was to determine the incidence of postoperative complications and the occurrence of myopic shift in infantile eyes after cataract surgery and implantation of an intraocular lens (IOL). METHODS: Cataract surgery and IOL implantation was performed on 11 infants with unilateral congenital cataracts who had a mean age of 10+/-6 weeks at 5 clinical centers. IOLs with a mean power of 26.2+/-2.3 D were implanted using a standardized protocol. The infants were then followed up for a mean of 13+/-6 months for postoperative complications and longitudinal changes in their refractive error. RESULTS: Eight of the 11 eyes had postoperative complications and were treated with a reoperation. Complications included open-angle glaucoma (n = 2), lens reproliferation into the visual axis (n = 2), pupillary membranes (n = 2), and corectopia (n = 2). A younger age at the time of surgery was positively correlated with the development of a postoperative complication requiring a reoperation (P = .03). A mean myopic shift of 5.49 D occurred in these eyes a year after surgery. No preoperative factors could be identified that correlated with the magnitude of the myopic shift. CONCLUSION: IOL implantation during infancy is associated with a high complication rate frequently requiring reoperation. A large myopic shift typically occurs that necessitates an initial or a late overcorrection with spectacles or a contact lens, depending on the power of the IOL implanted. Until ongoing randomized trials are completed, we recommend that surgeons exercise caution before implanting IOLs in the eyes of infants.

Age Factors↗
PubMed1999

In-the-bag secondary intraocular lens implantation in children.

BACKGROUND: Surgery for congenital cataracts in early infancy usually includes a primary posterior capsulectomy and an anterior vitrectomy. Initially, most of these infants have aphakia after surgery. Over time, remaining equatorial lens epithelial cells produce new cortical fibers, resulting in a ring of cortex trapped between the lens equator and the fused anterior and posterior capsulectomy edges. A potential space is maintained between the anterior and posterior capsular leaflets. We describe a technique for placing a secondary intraocular lens (IOL) within the capsular bag. PATIENTS AND METHODS: Eight children, ranging in age from 11 months to 14 years, who originally had aphakia after cataract extraction were operated on with the intent to reopen the capsular bag and place an IOL in the bag. RESULTS: Secondary in-the-bag IOL implantation was successfully completed in 7 of 8 children. This was accomplished by reopening the capsular bag 360 degrees at the edge of the fused anterior and posterior capsulectomy remnants, using the previously published vitrectorhexis technique. Residual cortical material was aspirated, and an IOL was placed within the capsular bag. In 1 child, aged 14 years, the capsular bag was reopened, but the lens was placed in the ciliary sulcus because the new anterior capsule edge could not be visualized for 360 degrees . CONCLUSION: Placement of secondary IOLs within the capsular bag can be accomplished successfully for selected patients in the pediatric population. Surgeons operating on infantile cataracts without primary IOL placement can facilitate capsular IOL sequestration later by limiting the anterior and posterior capsulectomy to 4 to 5 mm and performing a generous anterior vitrectomy to help prevent secondary closure of the smaller capsulectomy.

Adolescent↗
PubMed1999

Rupture of the anterior lens capsule in Alport syndrome.

Alport syndrome is an inherited disorder of type IV collagen, a major constituent of basement membranes. Eighty-five percent of cases are transmitted through X-linked dominant inheritance, although autosomal dominant and autosomal recessive inheritance has also been reported. Clinical manifestations of Alport syndrome include progressive glomerulopathy, sensorineural deafness, anterior lenticonus, posterior corneal dystrophy, and abnormal retinal pigmentation. Anterior lenticonus may lead to loss of vision because of progressive myopia or cataract formation. We report 2 cases of unusual cataract formation in adolescent boys who had a rupture of the anterior lens capsule. One rupture was spontaneous, and the other was traumatic.

Adolescent↗
PubMed1999

Effects of lifelong moderate caloric restriction on levels of neuropeptide Y, proopiomelanocortin, and galanin mRNA.

We are interested in how neuropeptides that regulate both food intake and reproductive function change with age and how life-prolonging moderate caloric restriction may influence the expression of these neuropeptides. We measured neuropeptide Y (NPY) and proopiomelanocortin (POMC) mRNA in the arcuate nucleus (AN), and galanin (GAL) mRNA in the AN, paraventricular nucleus (PVN) and medial septum-diagonal band of Broca in young, middle-aged and old female rats on a controlled feeding regimen. Female Sprague-Dawley rats (7 weeks old) were placed on caloric restriction (CR; n = 70) which was 60% of ad libitum (AL) intake measured in control rats (n = 70). Rats were rapidly decapitated 2.5 weeks following ovariectomy, when they were 4, 12, or 18 months old. Brains were frozen and coronal sections (12 microns) were cut at -20 degrees C using a cryostat. Relative levels of NPY, POMC and GAL mRNA were measured using in situ hybridization histochemistry. cDNA clones complementary to rat NPY, mouse POMC and rat GAL were used to synthesize 35S-UTP-labeled cRNA probes. Slides were dipped in photographic emulsion. Silver grains were quantified using computer-assisted image analysis. Caloric restriction increased NPY mRNA/cell, decreased POMC mRNA/cell in the AN, and did not influence GAL mRNA/cell. Age and caloric restriction did not influence the number of cells with detectable NPY mRNA, POMC mRNA or GAL mRNA. Reproductive status at the time of decapitation influenced both the level and the number of cells expressing GAL mRNA in the PVN. In summary, CR differentially affects levels of NPY, POMC and GAL mRNA in the AN. In this animal model, there was no statistically significant effect of age nor any interaction between age and diet on expression of any of these genes between 4 and 18 months of age.

Aging↗
PubMed1999

Cloning of the gene encoding the Actinobacillus actinomycetemcomitans serotype b OmpA-like outer membrane protein.

The gene encoding an outer membrane protein A (OmpA)-like, heat-modifiable Omp of Actinobacillus actinomycetemcomitans ATCC 43718 (strain Y4, serotype b) was cloned by a PCR cloning procedure. DNA sequence analysis revealed that the gene encodes a protein of 346 amino acid residues with a molecular mass of 36.9 kDa. The protein expressed by the cloned gene reacted with a monoclonal antibody to the previously described 29-kDa Omp (Omp29) of strain Y4. This monoclonal antibody reacted specifically with Omp29 of A. actinomycetemcomitans (serotype b), but not with any Omp of Escherichia coli, including OmpA. This protein exhibited characteristic heat modifiability on sodium dodecyl sulfate-polyacrylamide gels, showing an apparent molecular mass of 29 kDa when unheated and a mass of 34 kDa when heated. The N-terminal amino acid sequence of the protein expressed in E. coli perfectly matched those deduced from the purified Omp29 of strain Y4. The deduced amino acid sequence of the gene coding for Omp29 from serotype b matched completely (except for valine at position 321) that of a recently reported omp34 gene described for A. actinomycetemcomitans serotype c (NCTC 9710). Because of the conserved nature of the gene within these serotypes, we designated the gene described herein from serotype b as omp34.

Aggregatibacter actinomycetemcomitans↗
PubMed1999

Neuroendocrine influences and repercussions of the menopause.

In summary, the evidence that both the ovary and the brain are key pacemakers in the menopause is compelling. Our appreciation that estrogens are important neurotrophic and neuroprotective factors has grown rapidly. Future studies will allow us to better understand the ensemble of factors that interact to maintain regular reproductive cyclicity and how this precise dynamic balance changes with age. Furthermore, understanding how estrogen exerts trophic and protective actions should lead to its use as an important therapeutic agent in the maintenance of normal neural function during aging and after injury.

Aging↗
PubMed1999

Continuous s.c. infusion rather than twice-daily injections of IGF-I more effectively increases serum IGF binding protein-3 in female monkeys.

OBJECTIVE: In order to better understand how the IGF-I axis is affected by exogenous IGF-I, this study compared the effects of a constant s.c. infusion of IGF-I with that of twice-daily injections of IGF-I in young adult female rhesus monkeys. Clinical studies suggest that circulating concentrations of insulin-like growth factor binding protein-3 (IGFBP-3) are decreased or unaffected by IGF-I administration, whereas acute increases in IGF-I may increase serum IGFBP-1. However, studies in monkeys indicate that acute or continuous infusion of IGF-I effectively increases serum IGFBP-3. DESIGN AND METHODS: Female monkeys were studied for 5 days with no IGF-I supplementation (baseline) and for 5 days of IGF-I treatment by either constant infusion (120 microg/kg per day s.c., n = 5) or twice-daily injections of IGF-I (60 microg/kg per injection s.c., n = 5). Serum samples were collected daily at 0800 h and at 0800, 0900, 1100, 1500, and 2000 h on days 1 and 4 for each condition. Samples were assayed for IGF-I, IGFBPs-1 and -3, insulin, and glucose. RESULTS: Serum IGF-I was consistently increased above baseline within 24 h of the initiation of constant infusion, but was delayed until the second day of treatment in the injection group. Serum IGFBP-3 followed the pattern of IGF-I, with concentrations increased by day 1 during constant infusion and by day 2 during intermittent injections. Although both treatments effectively increased serum IGFBP-3, the increase was greater during constant infusion (31% above baseline) compared with injection (17%). Immunoblotting revealed that the constant infusion of IGF-I resulted in quantitatively more lower-molecular-mass fragments of IGFBP-3 than were observed during baseline or intermittent injections. Size-exclusion chromatography and ultrafiltration indicated that most IGFBP-3 was found in the ternary complex, with a greater percentage found in the ternary complex during baseline (90%) than during constant infusion (86%) or intermittent injections of IGF-I (87%). In contrast, serum concentrations of IGFBP-1 were increased on day 1 of both treatments, but declined towards baseline values as treatment progressed. Serum concentrations of insulin and glucose were unaffected by either mode of IGF-I treatment. Serum concentrations of IGF-I and IGFBP-3 were increased within 3h of the injection, before declining towards the pre-injection level. In contrast, the daily pattern of serum hormone concentrations was similar between the baseline condition and during constant infusion of IGF-I. Although higher during the treatment phase, serum IGF-I and IGFBP-3 concentrations decreased significantly from 0800 h until the afternoon meal, reaching a nadir in the evening before increasing again the next morning. Serum insulin decreased also after the morning meal and increased significantly immediately after the afternoon meal. Although serum IGFBP-1 also decreased initially after the morning meal, concentrations reached a peak before the afternoon meal as serum insulin reached its nadir. CONCLUSION: The results of the present analysis indicate that the constant infusion of IGF-I more effectively sustains serum concentrations of IGF-I and IGFBP-3 than do twice-daily injections. Although the percentage of IGF-I and IGFBP-3 in the ternary complex was similar during both treatments, the constant infusion regimen produced lower-molecular-mass fragments of IGFBP-3. In addition, serum IGF-I and IGFBP-3 appeared to be regulated diurnally, even during IGF-I infusion, whereas IGFBP-1 and insulin were affected by the timing of food intake. Taken together, these data suggest that, in the monkey, IGFBP-3 is regulated by factors in addition to GH, and that IGF-I can affect its own bioavailability by increasing circulating concentrations of IGFBP-3.

Animals↗
PubMed1999

The impacts of uterine environment and fetal genotype on conceptus size and placental vascularity during late gestation in pigs.

Meishan and Yorkshire gilts were bred exclusively to Yorkshire and Meishan boars, respectively, resulting in similar Meishan x Yorkshire fetuses gestating in the uteri of both maternal breeds. Gilts of both breeds were slaughtered on d 90 and 110 of gestation, and the weight and volume of each uterine horn was determined. Fetal weights and crown-rump lengths were recorded. A section of the chorioallantoic-endometrial attachment site was collected for each conceptus and evaluated for placental and endometrial vascular density. An intact placenta was recovered for each conceptus and weighed, and its surface area was determined. Fetal weight and crown-rump length increased (P < .001) markedly between d 90 and 110 of gestation in Meishan and in Yorkshire uteri, but they were markedly less (P < .001) in Meishan than in Yorkshire uteri. Placental weight and placental surface area were reduced by 40% in Meishan, compared with Yorkshire, uteri; however, placental size did not increase between d 90 and 110 in either uterine type. Placental vascular density and associated endometrial vascular density were similar (P > .20) for conceptuses in Meishan and Yorkshire uteri on d 90 and 110 of gestation. Additionally, even though the ratio of fetal weight: placental weight (placental efficiency) increased between d 90 and 110, placental efficiency was similar for conceptuses in Meishan and Yorkshire uteri. In a previous study using straightbred Meishan or Yorkshire conceptuses gestated in either a Meishan or Yorkshire uterus, we found Meishan conceptuses had a markedly greater placental efficiency than did Yorkshire conceptuses, regardless of the type of uterus in which they were gestated. These data indicate that uterine type determines conceptus size and conceptus genotype controls placental efficiency.

Animals↗
PubMed1999

Novel insight into the control of litter size in pigs, using placental efficiency as a selection tool.

Chinese Meishan pigs produce three to five more pigs per litter than less-prolific U.S. or European pig breeds as a result of a markedly decreased placental size and an increased pig weight: placental weight ratio (placental efficiency). We hypothesized that as a result of their intense selection for prolificacy, the Chinese had indirectly selected for a smaller, more efficient placenta in the Meishan breed. The goals of this study were to determine whether 1) significant variation in placental size and efficiency existed within our population of purebred Yorkshire pigs and 2) selection of pigs (boars and gilts) based on clear differences in placental size and efficiency would affect litter size. There was significant (approximately threefold) variation in placental efficiency in our herd of Yorkshire pigs, and marked (approximately twofold) variation existed within individual litters. We then selected pigs (boars and gilts) that had either a higher (A Group) or lower (B Group) than average placental efficiency. Although the birth weights of selected A Group pigs were similar to those of the B Group pigs, they had markedly smaller placentae. Males from each group (A or B) were bred to the females of the same group, and farrowing data were collected from parities 1 and 2. In both parities, A Group females farrowed more live pigs per litter than did B Group females (12.5 +/- .7 vs 9.6 +/- .5, P < .05). Although A Group pigs were on average approximately 20% lighter than B group pigs (1.2 +/- .1 vs 1.5 +/- .1 kg, P < .05), their placentae were approximately 40% lighter (250 +/- 10 vs 347 +/- 15 g, P < .01), resulting in a marked increase in placental efficiency. The results of this study suggest that selection on placental size and efficiency may provide a valuable tool for optimizing litter size in commercially important pig breeds.

Animal Husbandry↗
PubMed1999

Estradiol: a protective and trophic factor in the brain.

In recent years our appreciation that estradiol is truly a pleiotropic hormone has grown dramatically. We will review the findings that suggest that estrogens may exert important non-reproductive actions on the brain. These studies provide important insights into the clinical effects of estrogen replacement therapy on age- and disease-related processes in the brain. We will also discuss the multiple cellular and molecular mechanisms that may underlie estradiol's neurotrophic and neuroprotective effects.

Journal Article↗
PubMed1999

The Swedish family: transition to parenthood.

Family interaction during pregnancy and the transition to parenthood creates the social environment in which the fetus becomes part of the family, family relationships and roles are reorganized, and the infant's temperament appears. The purpose of this study was to examine the relationships among family dynamics, parental-fetal attachment, and infant temperament across the transition to parenthood. A sample of 91 families in Helsingborg, Sweden completed the Family Dynamics Measure and the Maternal/Paternal Fetal Attachment Scale during the third trimester of pregnancy. When the infant was 8-9 months old, mothers (n = 62) and fathers (n = 54) again completed the Family Dynamics Measure. The mother completed the Revised Infant Temperament Questionnaire as well. Overall, we found small changes in family dynamics, with an increase in perceived role conflict and mutuality reported by mothers. Fathers reported greater fetal attachment than their partners. Greater paternal- and maternal fetal attachment was related to more positive family dynamics, and maternal-fetal attachment was positively related to infant mood at 8 months. The stability of family dynamics across the transition to parenthood is a sign that most families negotiate this transition without difficulty.

Demography↗