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Biomedical subjects

C Howard

Publications and source records attributed to C Howard.

At least 19 recordsLinked to original sources
PubMed2002

Mycobacterium paratuberculosis heat shock protein 70 as a tool in control of paratuberculosis.

Paratuberculosis in cattle is a chronic intestinal disease in which a distinctive cellular reactivity of a Th1-type preceeds the phase in which antibody titers are easily detectable and the animal becomes clinically ill. During infection with Mycobacterium avium ssp. paratuberculosis (M.a.p), a decrease in CD4 T-helper cells has been observed in the clinical phase. Our ultimate aim is to elicit a cytotoxic reaction against infected macrophages, using recombinant Hsp70 (rHsp70) of M.a.p. as a tool to shuttle antigen into the MHC class I antigen presentation pathway. To investigate the mechanism of rHsp70 as a carrier for antigen into the cell, we studied the interaction between APC and Fitc-labelled rHsp70, using FACS analysis and confocal microscopy. Interaction of rHsp70 with the cell surface of bovine APC, presumably via a receptor, was shown on monocytes, monocyte derived macrophages and dendritic cell (DC). The interaction is detectable on the complete population of freshly derived monocytes, although peak intensity of fluorescence is lower on these cells than on macrophages and DCs. DCs show interaction on a high percentage of the cells, with high intensity, while in the case of macrophages only a subpopulation interacts with rHsp70. Efficient uptake of rHsp70 as compared to OVA is shown. Preincubation of DC with unlabelled rHsp70 leads to a decreased interaction with rHsp70-FITC. DC interacting with rHsp70 in addition showed high expression of MHC I, MHC II, Myd-1 (CD172a) and CD40. Further research will focus on loading of the rHsp70 with M.a.p. antigen for presentation in MHC class I.

Animals↗
PubMed2002

Characterization of humoral and cellular immune responses elicited by meningococcal carriage.

In order to study the immune response elicited by asymptomatic carriage of Neisseria meningitidis, samples of serum, peripheral blood mononuclear cells (PBMCs), and saliva were collected from a cohort of more than 200 undergraduate students in Nottingham, United Kingdom, who were subject to high rates of acquisition and carriage of meningococci. Serum immunoglobulin G levels were elevated following increases in the rate of carriage, and these responses were specific for the colonizing strains. In order to investigate T-cell responses, PBMCs from 15 individuals were stimulated with a whole-cell lysate of the H44/76 meningococcal strain (B:15:P1.7,16), stained to detect cell surface markers and intracellular cytokines, and examined by flow cytometry. The cells were analyzed for expression of CD69 (to indicate activation), gamma interferon (IFN-gamma) (a representative T-helper 1 subset [Th1]-associated cytokine), and interleukin-5 (IL-5) (a Th2-associated cytokine). Following a brief meningococcal stimulation, the numbers of CD69(+) IFN-gamma(+) CD56/16(+) NK cells were much higher than cytokine-positive CD4(+) events. Both IFN-gamma(+) and IL-5(+) events were detected among the CD69(+) CD4(+) population, leading to the conclusion that an unbiased T-helper subset response was elicited by meningococcal carriage.

Antibodies, Bacterial↗
PubMed2002

The anatomy of tibial eminence fractures: arthroscopic observations following failed closed reduction.

BACKGROUND: Failed manipulative reduction of avulsion fractures of the tibial insertion of the anterior cruciate ligament has been attributed to interposition of soft tissues, particularly the anterior horn of the medial meniscus. The objectives of the present report were (1) to show that the failure to reduce Meyers and McKeever type-III tibial eminence fractures was not due to interposition of soft tissues and (2) to discuss the relevance of the finding that the anterior third of the lateral meniscus was attached to the avulsed anterior cruciate ligament insertion site in all patients studied. METHODS: Twelve patients who had had a failed manipulative reduction of a type-III tibial eminence fracture underwent arthroscopic reduction and fixation of the avulsed fragment. RESULTS: A number of consistent findings were noted. The avulsed intercondylar eminence was displaced superiorly into the intercondylar notch. Attached to this fragment was not only the anterior cruciate ligament, but also, in all cases, the anterior horn of the lateral meniscus. The anterior third of the lateral meniscus had been torn from its tibial attachment and displaced together with the osseous fragment into the intercondylar notch. No interposition of bone or soft tissue was observed. Reduction of the osseous fragment was facilitated by traction on, or sutures passed around, the anterior horn of the lateral meniscus. Standard fixation methods were utilized. CONCLUSIONS: The concept that avulsion fractures of the tibial insertion of the anterior cruciate ligament cannot be reduced by manipulation because of soft-tissue interposition was not supported by the findings of the present study. The attachment of the anterior horn of the lateral meniscus to the avulsed tibial insertion of the anterior cruciate ligament may not be an irrelevant incidental finding. The observation that the displaced osseous fragment was attached simultaneously to the anterior cruciate ligament and to the anterior horn of the lateral meniscus, both pulling in different directions, may explain why type-III tibial eminence fractures are irreducible by manipulation.

Adolescent↗
PubMed2001

Economic analysis as a basis for large-scale nitrogen control decisions: reducing nitrogen loads to the Gulf of Mexico.

Economic analysis can be a guide to determining the level of actions taken to reduce nitrogen (N) losses and reduce environmental risk in a cost-effective manner while also allowing consideration of relative costs of controls to various groups. The biophysical science of N control, especially from nonpoint sources such as agriculture, is not certain. Widespread precise data do not exist for a river basin (or often even for a watershed) that couples management practices and other actions to reduce nonpoint N losses with specific delivery from the basin. The causal relationships are clouded by other factors influencing N flows, such as weather, temperature, and soil characteristics. Even when the science is certain, economic analysis has its own sets of uncertainties and simplifying economic assumptions. The economic analysis of the National Hypoxia Assessment provides an example of economic analysis based on less than complete scientific information that can still provide guidance to policy makers about the economic consequences of alternative approaches. One critical value to policy makers comes from bounding the economic magnitude of the consequences of alternative actions. Another value is the identification of impacts outside the sphere of initial concerns. Such analysis can successfully assess relative impacts of different degrees of control of N losses within the basin as well as outside the basin. It can demonstrate the extent to which costs of control of any one action increase with the intensity of application of control.

Agriculture↗
PubMed2001

Outcome of growth hormone therapy in children with growth hormone deficiency showing an inadequate response to growth hormone-releasing hormone.

Saizen (recombinant growth hormone [GH]), 0.2 mg/(kg x wk), was given in an open-label fashion for an average of 51 mo to 27 children with presumed idiopathic GH deficiency who had withdrawn from a trial of Geref (recombinant GH-releasing hormone [GHRH] 1-29) because of inadequate height velocity (HV) (25 children), the onset of puberty (1 child), or injection site reactions (1 child). Measurements were made every 3-12 mo of a number of auxologic variables, including HV, height standard deviation score, and bone age. The children in the study showed excellent responses to Saizen. Moreover, first-year growth during Saizen therapy was inversely correlated with the GH response to provocative GHRH testing carried out 6 and 12 mo after the initiation of Geref treatment. These findings indicate that GH is effective in accelerating growth in GH-deficient children who do not show or maintain a satisfactory response to treatment with GHRH. In addition, they suggest that the initial response to GH therapy used in this way can be predicted by means of provoc-ative testing.

Adolescent↗
PubMed2000

Office prenatal formula advertising and its effect on breast-feeding patterns.

OBJECTIVE: To compare the effect of formula company-produced materials about infant feeding to breast-feeding promotion materials without formula advertising on breast-feeding initiation and duration. METHODS: Five hundred forty-seven pregnant women were randomized to receive either formula company (commercial; n = 277) or specially designed (research; n = 270) educational packs about infant feeding at their first prenatal visit. Feeding method was determined at delivery. Breast-feeding duration of the 294 women who chose to breast-feed was ascertained at 2, 6, 12, and 24 weeks. Survival analyses were used to evaluate continuous outcomes, and chi2 and logistic regression analyses were used to evaluate discrete outcomes. RESULTS: Breast-feeding initiation (relative risk [RR] 0.93, 95% confidence interval [CI] 0.61, 1.43) and duration after 2 weeks (hazard ratio 1.19, 95% CI 0.86, 1.64) were not affected. Women in the commercial group were more likely to cease breast-feeding before hospital discharge (RR 5.80, 95% CI 1.25, 54.01) and before 2 weeks (adjusted odds ratio [OR] 1.91, 95% CI 1.02, 3.55). In subgroup analyses, women with uncertain goals for breast-feeding or goals of 12 weeks or less experienced shortened exclusive (hazard ratio 1.53, 95% CI 1.06, 2.21), full (hazard ratio 1.70, 95% CI 1.18, 2.48), and overall (hazard ratio 1.75, 95% CI 1.16, 2.64) breast-feeding duration when exposed to the commercial intervention. CONCLUSION: Although breast-feeding initiation and long-term duration were not affected, exposure to formula promotion materials increased significantly breast-feeding cessation in the first 2 weeks. Additionally, among women with uncertain goals or breast-feeding goals of 12 weeks or less, exclusive, full, and overall breast-feeding duration were shortened. Educational materials about infant feeding should support unequivocally breast-feeding as optimal nutrition for infants; formula promotion products should be eliminated from prenatal settings.

Adult↗
PubMed2000

Glucocorticoid-induced osteopenia in adolescent heart transplant recipients.

BACKGROUND: Glucocorticoid-induced cushingoid symptoms, including osteopenia and osteoporosis are well-documented in adult heart transplant recipients (HTR). Bone mineral density (BMD) of the axial skeleton is diminished by 10% to 20% within 60 days after transplantation (Tx) and most adult HTR fulfill World Health Organization criteria for osteoporosis (BMD > 2.5 SD below norm). At present, we do not know whether glucocorticoids have similar deleterious effects in adolescent HTR. METHODS: To determine the consequences of glucocorticoid immunosuppression on regional bone mineral density (BMD) and biochemical markers of bone metabolism in adolescent HTR, we studied 19 patients (aged 16 +/- 3) at 19 months (group mean) after Tx. We measured BMD (hydroxyapatite g/cm(2)) of the total body, lumbar spine, and pelvis using dual-energy X-ray absorptiometry (Lunar). Serum levels of bone-specific alkaline phosphatase and pyridinoline cross-links were determined by enzyme immunoassay in serum kits. RESULTS: The BMD of the lumbar spine (-12%), femur neck (-13%), femur trochanter (-12%), and ward's triangle (-16%) were significantly (p < 0.05) lower in adolescent HTR than age- and gender-matched norms. Serum levels of alkaline phosphatase (29 +/- 6 vs 22 +/- 3 U/liter) and pyridinoline cross-links (5.3 +/- 1.1 vs 3.8 +/- 0.7 mmol/liter) were significantly (p < 0.05) elevated in adolescent HTR, compared with age- and gender-matched controls studied in our laboratory. CONCLUSIONS: Our cross-sectional results demonstrate that BMD of the axial skeleton in adolescent HTR is significantly lower (-10% to 20%) than age-matched norms and that serum biochemical markers of bone metabolism are significantly elevated, suggesting accelerated bone turnover.

Absorptiometry, Photon↗
PubMed2000

Adhesions from flexor tendon surgery: an animal study comparing surgical techniques.

Intraoperative and postoperative hemorrhage has long been considered a cause of tendon adhesion and, thus, scarring and poor surgical results. To prevent such problems bipolar coagulators are commonly used during surgery to help achieve hemostasis. Surgical lasers also have been reported to help limit bleeding and scar formation. Very little is known regarding the relationship between hemorrhage and/or direct tendon tissue effects and tendon adhesions with the use of these modalities. We compared 3 different surgical techniques (meticulous sharp scalpel dissection, scalpel dissection plus bipolar coagulation, and CO(2) laser dissection) and used chicken flexor tendons to biomechanically and histologically assess the amount of adhesion formation after each procedure. Our findings show that bipolar coagulation and CO(2) laser application are both associated with significantly increased adhesion formation in tendon surgery compared with sharp dissection alone and that the meticulous, conventional sharp dissection technique is the best method to control adhesion formation. These conclusions have relevance to clinical tendon surgery.

Animals↗
PubMed2000

The changing focus of mental health nursing in east London.

The focus of care for Community Mental Health Nurses (CMHNs) has been moving towards the Severely Mental Ill (SMI) client group over the past ten years. Government guidelines and nursing literature indicate that SMI clients have been neglected in the past and that CMHNs should now prioritize this client group. This paper attempts to define the term SMI and to ascertain whether or not CMHNs in three east-London boroughs are prioritizing this client group. The opinions of these CMHNs are also given in relation to the specific new education and training required to work with this client group. We found that CMHNs were conscious of a distinct shift in focus towards SMI clients, but that they often felt inadequately trained for this change in focus. Recommendations are made for the future training and education of CMHNs to enable them to work with SMI clients more effectively.

Clinical Competence↗
PubMed1999

HIV-associated immune dysfunction and delayed pubertal development in a cohort of young hemophiliacs. Hemophilia Growth and Development Study.

As part of the Hemophilia Growth and Development Study (HGDS), we investigated the relationship between HIV-associated immune dysfunction and delayed pubertal development in a cohort of 333 boys and adolescents with moderate or severe hemophilia who were between the ages of 6 and 19 years at study entry in 1989. Sixty-two percent of the cohort was infected with HIV in the late 1970s and early 1980s through exposure to contaminated clotting factor concentrates. The cohort was observed during follow-up at 6-month intervals; measurements taken at each follow-up visit included Tanner stage and CD4+ cell count. This analysis of data from the first 4 years of follow-up revealed statistically significant delays in pubertal development associated with increasing levels of immune dysfunction. Our results emphasize the importance of following pubertal development in HIV-infected adolescent boys since delays in maturation may reflect underlying disease progression.

Adolescent↗
PubMed1999

X-chromosome inactivation patterns do not implicate asymmetric splitting of the inner cell mass in the aetiology of twin-twin transfusion syndrome.

The aetiology of twin-twin transfusion syndrome (TTTS) is unclear. We investigated the hypothesis that monochorionic (MC) pregnancies with TTTS are associated with differences in the timing and symmetry of twinning compared to MC twin pregnancies without TTTS. DNA was extracted from the umbilical cord vessels of 26 female MC twins, 14 with and 12 without TTTS on serial antenatal ultrasound. X-inactivation patterns were determined by DNA digestion with Hhal and Hpall followed by polymerase chain reaction for a polymorphic trinucleotide repeat in the androgen receptor gene. Products were quantified by densitometry and results compared to those in peripheral blood samples of adult female controls. The median degree of non-random inactivation was similar in MC twins with TTTS, in MC twins without TTTS, and in adult controls. The percentage of individuals with skewed (> or =30/70%) inactivation patterns was no different in MC twins with TTTS compared to those without TTTS, and was similar to adult controls using either enzyme technique. In conclusion we found no difference in the degree or frequency of non-random X-inactivation patterns in TTTS. X-inactivation patterns do not appear to be a useful tool for studying the symmetry of inner cell mass splitting in monochorionic twins.

Adult↗
PubMed1999

Primary prevention of childhood lead exposure: A randomized trial of dust control.

BACKGROUND: Dust control is recommended as one of the primary strategies to prevent or control children's exposure to residential lead hazards, but the effect of dust control on children's blood lead levels is poorly understood. OBJECTIVE: To determine the effectiveness of dust control in preventing children's exposure to lead, as measured by blood lead levels, during their peak age of susceptibility. DESIGN: A randomized, controlled trial. SETTING: Rochester, NY. PARTICIPANTS: A total of 275 urban children were randomized at 6 months of age, of whom 246 (90%) were available for the 24-month-old follow-up visit. INTERVENTIONS: Children and their families were randomly assigned to an intervention group (n = 140), which received cleaning equipment and up to eight visits by a dust control advisor, or a control group (n = 135). OUTCOME MEASURES: Geometric mean blood lead levels and prevalence of elevated blood lead levels (ie, >10 microg/dL, 15 microg/dL, and 20 microg/dL). RESULTS: At baseline, children's geometric mean blood lead levels were 2.9 microg/dL (95% confidence interval [CI] = 2.7, 3.1); there were no significant differences in characteristics or lead exposure by group assignment, with the exception of water lead levels. For children in the intervention group, the mean number of visits by a dust control advisor during the 18-month study period was 6.2; 51 (36%) had 4 to 7 visits, and 69 (49%) had 8 visits. At 24 months of age, the geometric mean blood lead was 7.3 microg/dL (95% CI = 6.6, 8.2) for the intervention group and 7.8 microg/dL (95% CI = 6.9, 8. 7) for the control group. The percentage of children with a 24-month blood lead >/=10 microg/dL, >/=15 microg/dL, and >/=20 microg/dL was 31% versus 36%, 12% versus 14%, and 5% versus 7% in the intervention and control groups, respectively. CONCLUSIONS: We conclude that dust control, as performed by families and in the absence of lead hazard controls to reduce ongoing contamination from lead-based paint, is not effective in the primary prevention of childhood lead exposure.

Dust↗
PubMed1998

Overview of the Second International Workshop to define swine cluster of differentiation (CD) antigens.

The aim of the Second International Swine Cluster of Differentiation (CD) Workshop, supported by the Veterinary Immunology Committee (VIC) of the International Union of Immunological Societies (IUIS), was to standardize the assignment of monoclonal antibodies (mAb) reactive with porcine leukocyte differentiation antigens and to define new antibody clusters. At the summary meeting of the workshop in July, 1995, revisions in the existing nomenclature for Swine CD were approved, so that the rules are now in accord with those for human and ruminant CD. Swine CD numbers will now be given to clusters of mAb to swine orthologues of human CD molecules when homology is proven by (1) suitable tissue distribution and lymphoid cell subset expression, (2) appropriate molecular mass of the antigen recognized by the mAbs, and (3) reactivity of mAbs with the cloned swine gene products, or cross-reactivity of the mAb on the human gene products. In some cases, this reactivity would not be fully proven, mainly due to the lack of cloned gene products; for these CD antigens, the respective clusters will be assigned by the prefix 'w' which will lead to 'wCD' antigens. As a result of the Second International Swine CD Workshop the assignment of 16 mAb to existing CD groups (CD2a, CD4a, CD5a, wCD6, wCD8, CD14, CD18a, wCD21, wCD25) was confirmed, and 2 mAb to existing swine workshop clusters (SWC). More importantly, for the work on the porcine immune system, was the definition of 5 new swine CD antigens, namely CD3 (recognized by 6 new mAb and 3 epitopes), CD16 (1 new mAb), wCD29 (2 mAb), CD45RA (3 mAb) and CD45RC (1 new mAb). Finally, the demarcation of two new SWC molecules in swine, SWC8 (2 mAb) and SWC9 (2 mAb) was confirmed.

Animals↗