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M Howard

Publications and source records attributed to M Howard.

At least 37 records · Page 2Linked to original sources
PubMed2000

Comparison of self-collected vaginal, vulvar and urine samples with physician-collected cervical samples for human papillomavirus testing to detect high-grade squamous intraepithelial lesions.

BACKGROUND: Certain types of human papillomavirus (HPV) in cervical samples are strongly associated with squamous intraepithelial lesions (SIL) and invasive cervical carcinoma. We determined and compared the test characteristics of testing for HPV with samples obtained by patients and with samples obtained by their physicians. METHODS: In a consecutive series of women referred to a colposcopy clinic at a teaching hospital because of abnormalities on cervical cytologic screening, 200 agreed to collect vulvar, vaginal and urine samples for HPV testing. The physician then collected cervical samples for HPV testing, and colposcopy, with biopsy as indicated, was performed. Presence of HPV was evaluated using the hybrid capture II assay (Digene Corp., Silver Spring, Md.) with a probe cocktail for 13 carcinogenic types. Cervical specimens were also tested for HPV by polymerase chain reaction and hybridization with type-specific probes. Cervical smears for cytologic examination were obtained from all women. RESULTS: High-grade lesions (high-grade squamous intraepithelial lesions [HSIL], equivalent to cervical intraepithelial neoplasia [CIN] grade 2 or 3, and adenocarcinoma) were found in 58 (29.0%) of the 200 women. Carcinogenic types of HPV were detected in the self-collected vaginal samples of 50 (86.2%) of these 58 women, in the self-collected vulvar samples of 36 (62.1%) and in the self-collected urine samples of 26 (44.8%). Carcinogenic types of HPV were detected in the cervical samples collected by physicians for 57 (98.3%) of these 58 women. The remaining 142 women (71.0%) had normal findings or low-grade squamous intraepithelial lesions (LSIL, CIN grade 1). Test results were negative or noncarcinogenic types of HPV were detected in the self-collected vaginal samples of 76 (53.5%) of these 142 women, in the self-collected vulvar samples of 89 (62.7%) and in the self-collected urine samples of 99 (69.7%). The sensitivity for self-collected samples ranged from 44.8% to 86.2%, and the specificity from 53.5% to 69.7%. For the samples collected by physicians, the sensitivity was 98.3% and the specificity 52.1%. The self-sampling methods were generally acceptable to the women: 98.4% of respondents (126/128) deemed urine sampling acceptable, 92.9% (118/127) found vulvar sampling acceptable, and 88.2% (112/127) found vaginal sampling acceptable. INTERPRETATION: Self-collection of samples for HPV testing was acceptable to women attending a colposcopy clinic for investigation of suspected cervical lesions and shows sufficient sensitivity to warrant further evaluation as a screening test for cervical cancer prevention programs.

Adenocarcinoma↗
PubMed2000

Physical characterization of the MUC5AC mucin: a highly oligomeric glycoprotein whether isolated from cell culture or in vivo from respiratory mucous secretions.

We have isolated the high-M(r) mucins from growth medium of the early stage of an HT-29 cell culture by gel chromatography and isopycnic density gradient centrifugation. The mucins (buoyant density 1.34-1.44 g/ml) were reactive with an anti-peptide antiserum (MAN-5ACI) raised against a sequence from within the MUC5AC mucin. Similar antisera raised against the MUC2 and MUC5B mucins were not reactive. The MUC5AC reduced-mucin subunits exhibited a homogeneous charge distribution on anion-exchange chromatography, but appeared as two bands, one major and one more minor, after agarose gel electrophoresis. The unreduced mucins had an average M(r) in excess of 40 MDa and were visualized in the electron microscope as large, fine filamentous threads (many microns in length) that after reduction were greatly reduced in size (number average length 570 nm). Agarose gel electrophoresis of unreduced MUC5AC mucins identified a major band just entering the gel with evidence of a 'ladder' of faster-migrating minor bands. Partial reduction of the mucins increased the proportion of the faster bands and at least 16 could be discriminated. M(r) measurements showed that these bands differed by single monomer units. The mucins behaved as very stiff extended structures in solution and this characteristic might explain the poor separation of different-sized oligomers in sedimentation-rate experiments. The cell-culture mucin preparation had similar characteristics of charge and buoyant density to MUC5AC mucins from respiratory secretions in vivo. In addition the MUC5AC mucin from respiratory tract secretions exhibited similar behaviour, reduced and unreduced on agarose gel electrophoresis, indicating that the mucin has a similar molecular phenotype in vivo and in vitro.

Cell Line↗
PubMed2000

Effect of preventive home visits by a nurse on the outcomes of frail elderly people in the community: a randomized controlled trial.

BACKGROUND: Timely recognition and prevention of health problems among elderly people have been shown to improve their health. In this randomized controlled trial the authors examined the impact of preventive home visits by a nurse compared with usual care on the outcomes of frail elderly people living in the community. METHODS: A screening questionnaire identified eligible participants (those aged 70 years or more at risk of sudden deterioration in health). Those randomly assigned to the visiting nurse group were assessed and followed up in their homes for 14 months. The primary outcome measure was the combined rate of deaths and admissions to an institution, and the secondary outcome measure the rate of health services utilization, during the 14 months; these rates were determined through a medical chart audit by a research nurse who was blind to group allocation. RESULTS: The questionnaire was mailed to 415 elderly people, of whom 369 (88.9%) responded. Of these, 198 (53.7%) were eligible, and 142 consented to participate and were randomly assigned to either the visiting nurse group (73) or the usual care group (69). The combined rate of deaths and admissions to an institution was 10.0% in the visiting nurse group and 5.8% in the usual care group (p = 0.52). The rate of health services utilization did not differ significantly between the 2 groups. Influenza and pneumonia vaccination rates were significantly higher in the visiting nurse group (90.1% and 81.9%) than in the usual care group (53.0% and 0%) (p < 0.001). INTERPRETATION: The trial failed to show any effect of a visiting nurse other than vastly improved vaccination coverage.

Aged↗
PubMed2000

Universal PCR amplification of mouse immunoglobulin gene variable regions: the design of degenerate primers and an assessment of the effect of DNA polymerase 3' to 5' exonuclease activity.

Degenerate primers were designed for PCR amplification of unknown mouse immunoglobulin (Ig) light (L) and heavy (H) chain variable (V) genes. Each subgroup of mouse Ig gene sequences [Kabat, E.A., Wu, T. T., Perry, H.H., Gottesman, K.S., Foeller, C., 1991. Sequences of Proteins of Immunological Interest, 5th edn. US Department of Health and Human Services, Public Health Service, NIH.] was analyzed, and highly degenerate primers in the framework one (FR1) region were designed. A single highly degenerate FR1 primer sufficed for the amplification of light chains; for heavy chains, a series of FR1 primers was used. At the same time, we assessed the effect of 3' to 5' exonuclease activity of DNA polymerase on the utilization of these degenerate primers. Using Taq polymerase, which lacks 3' to 5' exonuclease activity, we successfully amplified the Ig VL and VH genes expressed in more than a hundred monoclonal hybridoma cell lines reactive against a phosphonamidate hapten. Sequence analysis of the cloned VL and VH genes, 52 of each, showed that they are derived from multiple germline families (10 of the 17 VL families and 9 of the 14 VH families) as recently defined [Martinez, C., Lefranc, M., 1998. The mouse (Mus musculus) immunoglobulin kappa variable (IGKV) genes and joining (IGKJ) segments. Exp. Clin. Immunogenet. 15, 184.]. The universality of our primers was also demonstrated by successful amplification of other mouse hybridoma cell lines that are specific to different antigens.

Animals↗
PubMed2000

Early myeloid cells are high producers of nitric oxide upon CD40 plus IFN-gamma stimulation through a mechanism dependent on endogenous TNF-alpha and IL-1alpha.

Bone marrow contains nonadherent low-density wheat germ agglutinin-positive (Fr3-WGA(+)) cells that release large amounts of NO and show natural suppressor activity if stimulated with activated T cells. We have assessed the involvement of CD40-derived signals in NO production and their cytokine requirements. Production of NO by Fr3-WGA(+) cells in co-culture with activated T cells is inhibited by a competing CD40 soluble fusion protein. Fr3-WGA(+) cells express the inducible NO synthase (iNOS) and release NO following CD40 plus IFN-gamma activation. Production of NO through CD40 is strictly dependent on endogenous TNF-alpha and / or IL-1alpha, since it is inhibited by neutralizing these cytokines or blocking the TNF receptor (p55). Both cytokines are transcribed when Fr3-WGA(+) cells are stimulated by CD40 signaling plus IFN-gamma, although TNF-alpha remains below detection limits in stimulated Fr3-WGA(+) cell cultures. Phenotypic studies combined with data on intracellular iNOS expression and cell sorting indicate that NO-producing cells are CD40, CD31 (ER-MP12), CD11b (Mac-1)low, ER-MP20 (Ly-6C) and Gr-1 (Ly-6G) positive, consistent with myeloid progenitors. The results point to early myeloid cells as an important cell source of NO once triggered by activated T cells through CD40 and IFN-gamma-derived signals, in a mechanism involving the production of TNF-alpha and / or IL-1alpha.

Animals↗
PubMed2000

Trauma mannequin assessment of management skills of surgical residents after advanced trauma life support training.

BACKGROUND: We tested the effectiveness of Advanced Trauma Life Support (ATLS) training among surgical residents using a specially designed mannequin. MATERIALS AND METHODS: Thirty-two Postgraduate Year I surgical residents were randomly assigned to two groups of 16 each. By use of a trauma mannequin, the 32 residents' performances were scored using four trauma scenarios before 16 residents (ATLS group) completed a standard ATLS course. Performances were also scored after the ATLS course on another four trauma scenarios. The scores were standardized to a maximum of 20 for each scenario. Organized Approach scores with a range of 1 to 5, Priority scores ranging from 1 to 7, and global ratings of Honors, Pass, Borderline, or Fail were assigned for each clinical scenario. RESULTS: The pre-ATLS assessment scores were similar for both groups ranging between 9.4 +/- 3.5 and 11.4 +/- 2.9 for the ATLS group and between 10.2 +/- 3.8 and 11.4 +/- 3.9 for the non-ATLS group. The ATLS group scores ranged from 16.0 +/- 1.3 to 17.4 +/- 3.1 after the course and the non-ATLS group scores ranged from 11.4 +/- 4.2 to 12.9 +/- 4.0 (P < 0.05). Pre-ATLS Organized Approach scores were 2.9 +/- 1.0 and 2.7 +/- 1.1 (NS) for the ATLS and non-ATLS groups, respectively, with post-ATLS scores being significantly higher in the ATLS group (4.9 +/- 1.2 compared with 2.8 +/- 1.2 for the non-ATLS group, P < 0. 05). Initial Priority scores were also similar for both groups (3.2 +/- 1.4 for the ATLS group and 3.3 +/- 2.0 for the non-ATLS group). Post-ATLS Priority scores were significantly higher (6.4 +/- 1.4) in the ATLS group compared with 4.2 +/- 1.9 for the non-ATLS group (P < 0.05). The pre-ATLS global ratings were similar for both groups and post-ATLS there were 10 Honors ratings in the ATLS group and none for the control group. CONCLUSIONS: Using a trauma mannequin, for assessment, surgical residents completing the ATLS course demonstrated superior resuscitation skills compared with a non-ATLS group.

General Surgery↗
PubMed2000

A transient deficit of motion perception in human.

We studied the motion perception abilities in a young adult, SF, who had her right occipito-temporal cortices resected to treat epilepsy. Following resection, SF showed transient deficits of both first- and second-order motion perception that recovered to normal within weeks. Previous human studies have shown either first- or second n order motion deficits that have lasted months or years after cerebral damage. SF also showed a transient defect in processing of shape-from-motion with normal perception of shape from non-motion cues. Furthermore, she showed greatly increased reaction times for a mental rotation task, but not for a lexical decision task. The nature and quick recovery of the deficits in SF resembles the transient motion perception deficit observed in monkey following ibotenic acid lesions, and provides additional evidence that humans possess specialized cortical areas subserving similar motion perception functions.

Adult↗
PubMed2000

[Myocardial revascularization of the anterior descending artery with the classical technic of mammary anastomosis].

INTRODUCTION AND OBJECTIVES: To establish the results obtained with the classical technique of mammary anastomosis of the anterior descending artery. MATERIALS AND METHODS: Between January 1982 and July 1997, 154 patients received an anastomosis of the left internal mammary artery to the left anterior descending coronary artery with use of the classical technique (sternotomy and extracorporeal circulation). RESULTS: There was no operative mortality in our group, nor paraoperational myocardial infarction, nor cephalic vascular accidents. One (0.6%) patient had sternal wound infection, and another (0.6%) required another reoperation for postoperational bleeding. All (100%) were followed-up from 3-183 months (average 64. 4 months). Actuarial global survival at 5, 10 and 15 years was 95.6%+/-2.1; 92.1%+/-4 and 85.5+/- 7.5 respectively, and the actuarial probability of being free from cardiac death was 99%+/-0.9; 99% and 99%. The actuarial probability of being free from myocardial infarction was 99%+/-0.9; 99%+/-0.9 and 99%; and from angina was 95%+/-2.2; 86.9%+/-4.9 and 74.5%+/-12.2 at 5, 10 and 15 years.Finally, the actuarial probability of being free from reoperation was 99%+/-0.9; 99%; 99% and from angioplasty 96.9%+/-1.7; 91.4%+/-4.1; 91.4%+/-4.1 at 5, 10 and 15 years, respectively. The average hospital charges in the last 10% of the patients was U$ 6.200. CONCLUSIONS: Revascularization of the left anterior descending with the left internal mammary artery and the classical technique (sternotomy and extracorporeal circulation) is a safe, minimal risk, effective, long lasting and cost efficient procedure with excellent results at 10 and 15 years.

Adult↗
PubMed2000

African American grandmothers' perceptions of caregiver concerns associated with rearing adolescent grandchildren.

In 1996, grandparents were the sole providers of care for 269,000 grandchildren. Research findings indicate that grandmothers are usually the primary caretakers of grandchildren. Previous issues associated with raising grandchildren vary, but usually relate to the grandparents' health, financial concerns, or lack of social support. This qualitative descriptive study was designed to describe African American grandmothers' perceptions about the burdens of raising adolescent grandchildren. Using this approach, the researchers were able to study the richness and diversity of the grandmothers' perceptions. Data were collected from 35 grandmothers through a focus group (n = 7) and during a 4-day intervention research study (n = 28) entitled "Grandmother-Grandchild Health Promotion Program." Numerous concerns were voiced by both groups, but those stated most frequently were associated with the well-being of grandchildren (grandchildren's sexual behavior, potential drug use, and potential risk of encountering violence) and relational conflicts with adult children. Unexpected findings were the absence of stated concerns associated with the grandmothers' financial situation or health. Recommendations for intervention, clinical practice, and research are discussed.

Adolescent↗
PubMed2000

Editorial overview

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Journal Article↗
PubMed2000

The role of autoantigens in autoimmune disease.

Many autoantigens have been identified in human patients and in rodent models. In numerous experimental settings, these autoantigens or related autoreactive lymphocytes can transfer autoimmunity. Although autoreactivity spreads to new epitopes during the course of disease, single-epitope-specific therapies show considerable efficacy in multi-epitope-induced models of autoimmunity. These observations may indicate that epitope-specific therapies operate at the level of regulating mechanisms of immune tolerance rather than exerting a direct effect on autoreactive T lymphocytes.

Animals↗
PubMed2000

The left atrial appendage: our most lethal human attachment! Surgical implications.

OBJECTIVES: To prevent death from atrial fibrillation, a cardiac disease which kills by producing emboli. Atrial fibrillation causes about 25% of strokes and increases stroke rate by five times. Over 90% of these embolic strokes are from clots originating in the left atrial appendage. This study addresses the surgical feasibility of removing the appendage to prevent future deaths in two subcategories of patients. (1) Prophylactic removal during open-heart surgery to study its safety. Theoretically, as these patients age and some develop atrial fibrillation, protection from embolic strokes would already be present. (2) Therapeutic removal in chronic atrial fibrillation patients by means of a thorascopic approach. Its technical feasibility is demonstrated. Its actual stroke prevention potential awaits large studies. METHODS: Appendectomy has been evaluated three ways. (1) Experimentally, thorascopic appendage removal was performed on 20 goats with endoscopic approach. Late studies showed a cleanly healed atrial closure after stapling, and no puckering of tissue as seen with the purse-string approach. (2) Safety of human appendectomy was demonstrated in 437 patients (1995-1997). Routine appendectomy was performed during open-heart surgery. Forty-three appendages were stapled, 391 sutured off. (3) Thorascopic appendectomy in seven patients with chronic atrial fibrillation has been successfully accomplished as an isolated surgical procedure. Stapling or suture closure provides a much cleaner, non-puckered suture line than a purse string. RESULTS: In prophylactic removal, no acute bleeding occurred. No late problems have been identified. Endoscopic removal of the appendage has been successful in seven atrial fibrillation patients. CONCLUSIONS: The left atrial appendage is a lethal source of emboli in atrial fibrillation patients. As patients age and often develop atrial fibrillation, prophylactic appendage removal whenever the chest is open is suggested as a method to prevent future strokes. In chronic atrial fibrillation patients, appendectomy can be done with a mini-thorascopic approach. Further studies are planned to demonstrate the effectiveness of appendectomy in preventing strokes in the chronic fibrillating patients.

Animals↗
PubMed2000

Chemokines in autoimmune diseases.

Autoimmune diseases like multiple sclerosis (MS) and insulin-dependent diabetes (IDD) are believed to be mediated by pathogenic CD4+ autoreactive T cells which mediate selective destruction of specific host cells. Interrupting the trafficking of such T cells from host circulation to the sites of pathology, such as the central nervous system in the case of MS and the pancreas in the case of IDD, potentially offers a novel opportunity for therapeutic intervention in these diseases. The following summarizes our evolving thoughts on the role of the chemokine network in MS and IDD, and focuses on the chemokine receptor CXCR3 as a potential target for impeding T-cell-mediated destruction in these disease settings.

Autoimmune Diseases↗
PubMed2000

Cyclin D2 is essential for BCR-mediated proliferation and CD5 B cell development.

Progression into G(1) in B lymphocytes is regulated by cyclins D2 and D3, components of the cell cycle machinery currently believed to have overlapping and potentially redundant roles in cell cycle control. To study the specific role of cyclin D2 in B lymphocyte proliferation, we examined B cells from cyclin D2(-/-) mice and demonstrate a specific requirement for cyclin D2 in BCR- but not CD40- or lipopolysaccharide-induced proliferation. Furthermore, conventional B cell development proceeds normally in the mutant mice; however, the CD5 B cell compartment is dramatically reduced, suggesting that cyclin D2 is important in CD5 B cell development as well as antigen-dependent B cell clonal expansion.

Animals↗
PubMed2000

Psychopathology, adversity, and service utilization of young refugees.

OBJECTIVE: To investigate the psychopathology, social impairment, adversities, and service utilization of refugee families and their children seeking help at a child and adolescent psychiatry clinic in London. METHOD: A retrospective case-control study of 30 refugee children and families individually matched with nonrefugee immigrant families and white British families. Case note review was carried out to obtain data on diagnosis, social adjustment, past adversity, exposure to violence, current socioeconomic circumstances, and use of the child and adolescent psychiatric service. RESULTS: Refugee children tended to have disorders with a psychosocial etiology rather than neurobiological disorders. Refugees had similar levels of social impairment compared with the other groups. Refugees were much more isolated and disadvantaged and had different referral pathways but were not more likely to drop out of treatment prematurely. CONCLUSIONS: Refugee children and families had been exposed to high levels of adversity. The ability of community agencies to refer families who could use treatment has significant resource implications.

Adolescent↗
PubMed2000

Surface critical behavior in systems with nonequilibrium phase transitions

We study the surface critical behavior of branching-annihilating random walks with an even number of offspring (BARW) and directed percolation (DP) using a variety of theoretical techniques. Above the upper critical dimensions d(c), with d(c)=4 (DP) and d(c)=2 (BARW), we use mean field-theory to analyze the surface phase diagrams using the standard classification into ordinary, special, surface, and extraordinary transitions. For the case of BARW, at or below the upper critical dimension d</=d(c), we use field theoretic methods to study the effects of fluctuations. As in the bulk, the field-theory suffers from technical difficulties associated with the presence of a second critical dimension. However, we are still able to analyze the phase diagrams for BARW in d=1 and 2, which turn out to be very different from their mean field analog. Furthermore, for the case of BARW only (and not for DP), we find two independent surface beta(1) exponents in d=1, arising from two distinct definitions of the order parameter. Using an exact duality transformation on a lattice BARW model in d=1, we uncover a relationship between these two surface beta(1) exponents at the ordinary and special transitions. Many of our predictions are supported using Monte Carlo simulations of two different models belonging to the BARW universality class.

Journal Article↗
PubMed2000

A new visual indicator of chlamydial cervicitis?

OBJECTIVES: To determine the usefulness of endocervical discharge opacity as a risk indicator for chlamydial infection in relation to two acknowledged visual indicators--yellow endocervical discharge and easily induced mucosal bleeding of the cervix. METHODS: Women from two family planning clinics, a therapeutic abortion clinic, and a university student health clinic (n = 1418 total) consented to a pelvic examination and chlamydia testing, and completed a questionnaire on socio-demographics, sexual behaviour, medical history, and symptoms. A case of chlamydia was defined as positive by culture or blocked enzyme immunoassay in an endocervical swab. RESULTS: The prevalence of chlamydial infection in the clinics was 6.3%. All three of the visual indicators--yellow endocervical discharge, easily induced bleeding, and opaque cervical discharge--were statistically significantly and independently associated with chlamydial infection (odds ratios 2.8, 2.3, and 2.9 respectively), independent of clinic type. Adjustment for the other visual indicators made little difference to the odds ratios. CONCLUSION: Opacity of endocervical discharge was at least as important as the other two commonly acknowledged indicators of chlamydial cervicitis--yellow endocervical discharge and easily induced mucosal bleeding of the cervix.

Adolescent↗