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Biomedical subjects

L Howard

Publications and source records attributed to L Howard.

At least 55 records · Page 3Linked to original sources

Home parenteral nutrition. 25 years later.

After 25 years, there is enough clinical outcome experience to determine appropriate use of home parenteral nutrition in different disease states and age groups. Information regarding how to avoid complications and how patients and families can find necessary psychosocial support is provided in this article. Currently, small bowel transplantation is not a safer choice, unless there is severe liver disease caused by home parenteral nutrition or lack of central intervenous access.

Gastrointestinal Diseases↗

Effects of antibodies to transferrin and alpha 2-HS glycoprotein on in vitro sperm motion: implications in infertility associated with endometriosis.

PROBLEM: Women with endometriosis have antibodies to endometrial transferrin and alpha 2-HS glycoprotein in their serum and peritoneal fluid. The objective of this study was to determine whether antibodies to transferrin and alpha 2-HS glycoprotein adversely affect sperm motility and survival. METHOD OF STUDY: Spermatozoa obtained from normal fertile donors and washed free of seminal plasma were incubated with the medium (control), 1:2 and 1:100 dilutions of antitransferrin, 1:4, 1:8 and 1:100 dilutions of anti-alpha 2-HS glycoprotein, and a 1:2 dilution of antialbumin antiserum (negative control). Sperm motion characteristics in 10 microliters aliquots were evaluated at 30 min, 1 hr, 2 hr, 4 hr, and 24 hr using computerized sperm motion analysis. A paired t-test was done to analyze the effects of the various antibodies on sperm motion characteristics. RESULTS: Antibodies to albumin failed to adversely affect sperm motility in general or the several sperm motion characteristics in particular. In contrast, antibodies to transferrin at the dilution of 1:2 adversely affected the percentage of motile and rapid spermatozoa, progressive and path velocities, straightness, linearity, track speed, and anterior-lateral head displacement (P < 0.001) at all the time intervals, whereas a 1:100 dilution of this antiserum adversely affected these parameters only at 24 hr. Elongation and beat cross-frequency were significantly affected at 4 and 24 hr by a 1:2 dilution of antitransferrin antiserum. The effects of anti-alpha 2-HS glycoprotein were more pronounced than those of antitransferrin, but they were similar. Dilutions of 1:4 and 1:8 were effective at all time intervals, whereas a 1:100 dilution was effective in reducing the track speed and the percentage of rapid cells at 24 hr (P < 0.001). CONCLUSION: Antibodies to endometrial transferrin and alpha 2-HS glycoprotein present in the peritoneal fluid, and possibly in the oviductal fluid, of patients with endometriosis may adversely affect postcoital sperm motility and sperm survival.

Antibodies↗

Schizophrenia and safety of parenting of infants: a report from a U.K. mother and baby service.

We discuss clinical issues associated with parenting in mothers with severe mental illness, in particular the safety of parenting and risk to infants. We also examine some of the implications for a young child of having as primary carer a mother who suffers from a chronic and severe mental illness. Types of clinical presentation, and assessment and management are described, with illustrative case examples.

Adult↗

Quantitative immunolocalization of a P29 protein (GRA7), a new antigen of toxoplasma gondii.

Ultrastructural localization of a P29 protein of Toxoplasma gondii was examined on thin sections by an immunogold technique using a P29 antigen-specific monoclonal antibody (5-241-178). Immunolocalization of the P29 protein in extracellular tachyzoites demonstrated that this antigen was present in the dense granules. Thus, we have identified this P29 antigen as the seventh protein (GRA7) to be localized to the dense granules of T. gondii. P29 immunolocalization in intracellular tachyzoites demonstrated association of this antigen with the parasite membrane complex, tubular elements of the intravacuolar network, and with the parasitophorous vacuolar membrane. Our immunolabeling data suggest trafficking of the P29 (GRA7) antigen from the dense granule via the intravacuolar network to the parasitophorous vacuolar membrane on invasion of the tachyzoite into the host cell. (J Histochem Cytochem 46:1411-1421, 1998)

Animals↗

Peer review and editorial decision-making.

INTRODUCTION: This paper describes and analyses the editor's decision-making process at the British Journal of Psychiatry (BJP), and investigates the association between reviewers' assessments and editorial decisions. METHOD: Four hundred consecutive manuscripts submitted over a six-month period to the BJP were examined prospectively for assessors' comments and editorial decisions on acceptance or rejection. Interrater reliability of assessments was calculated and a logistic regression analysis investigated the effect of the rank allocated by assessors and the comprehensiveness of the assessments on the editor's decision. RESULTS: The editor sent 248/400 (62%) manuscripts to assessors for peer review. Kappa for reliability of assessors rankings was 0.1 indicating poor interrater reliability. Assessors agreed best on whether to reject a paper. A ranking of five (indicating rejection) had the greatest association with editor's rejection (P < 0.001, odds ratio 0.079), and the mean ranking of assessments was also significantly associated with editorial acceptance or rejection (P = 0.004, odds ratio 0.24). CONCLUSION: Assessors and editors tend to agree on what is clearly not acceptable for publication but there is less agreement on what is suitable.

Decision Making↗

Outcome of long-term enteral feeding.

In the past two decades, many technical advances have made tube enteral feeding much more comfortable and acceptable to patients and their families. This has greatly expanded the use of this therapy, both in clinical conditions where it was traditionally prescribed and in many other diagnoses. This expanded use raises important questions about how much enteral nutrition is being used, the medical outcome in different clinical conditions, and the quality of life experienced by long-term therapy users. This article addresses these outcome issues for patients in the nonhospital setting.

Adaptation, Physiological↗

Transmembrane/cytoplasmic domain-mediated membrane type 1-matrix metalloprotease docking to invadopodia is required for cell invasion.

The invasion of human malignant melanoma cells into the extracellular matrix (ECM) involves the accumulation of proteases at sites of ECM degradation where activation of matrix metalloproteases (MMP) occurs. Here, we show that when membrane type 1 MMP (MT-MMP) was overexpressed in RPMI7951 human melanoma cells, the cells made contact with the ECM, activated soluble and ECM-bound MMP-2, and degraded and invaded the ECM. Further experiments demonstrated the importance of localization of the MT-MMP to invadopodia. Overexpression of MT-MMP without invadopodial localization caused activation of soluble MMP-2, but did not facilitate ECM degradation or cell invasiveness. Up-regulation of endogenous MT-MMP with concanavalin A caused activation of MMP-2. However, concanavalin A treatment prevented invadopodial localization of MT-MMP and ECM degradation. Neither a truncated MT-MMP mutant lacking transmembrane (TM) and cytoplasmic domains (DeltaTMMT-MMP), nor a chimeric MT-MMP containing the interleukin 2 receptor alpha chain (IL-2R) TM and cytoplasmic domains (DeltaTMMT-MMP/TMIL-2R) were localized to invadopodia or exhibited ECM degradation. Furthermore, a chimera of the TM/cytoplasmic domain of MT-MMP (TMMT-MMP) with tissue inhibitor of MMP 1 (TIMP-1/TMMT-MMP) directed the TIMP-1 molecule to invadopodia. Thus, the MT-MMP TM/cytoplasmic domain mediates the spatial organization of MT-MMP into invadopodia and subsequent degradation of the ECM.

Amino Acid Sequence↗

Identification of the 170-kDa melanoma membrane-bound gelatinase (seprase) as a serine integral membrane protease.

The 170-kDa membrane-bound gelatinase, seprase, is a cell surface protease, the expression of which correlates with the invasive phenotype of human melanoma and carcinoma cells. We have isolated seprase from cell membranes and shed vesicles of LOX human melanoma cells. The active enzyme is a dimer of N-glycosylated 97-kDa subunits. Sequence analysis of three internal proteolytic fragments of the 97-kDa polypeptide revealed up to 87.5% identity to the 95-kDa fibroblast activation protein alpha (FAPalpha), the function of which is unknown. Thus, we used reverse transcription-polymerase chain reaction to generate a 2.4-kilobase cDNA from LOX mRNA with FAPalpha primers. COS-7 cells transfected with this cDNA expressed a 170-kDa gelatinase that is recognized by monoclonal antibodies directed against seprase. Sequence analysis also showed similarities to the 110-kDa subunit of dipeptidyl peptidase IV (DPPIV). Like DPPIV, the gelatinase activity of seprase was completely blocked by serine-protease inhibitors, including diisopropyl fluorophosphate. Seprase could be affinity-labeled by [3H]diisopropyl fluorophosphate, but the proteolytically inactive 97-kDa subunit could not, confirming the existence of a serine protease active site on the dimeric form. Proteolytic activity is lost upon dissociation into its 97-kDa subunit following treatment with acid, heat, or cysteine and histidine-modifying agents. We conclude that seprase, FAPalpha, and DPPIV are related serine integral membrane proteases and that seprase is similar to DPPIV, the proteolytic activities of which are dependent upon subunit association.

Amino Acid Sequence↗

Surfaces modified with PEO by the Williamson reaction and their affinity for proteins.

Poly(ethylene oxide) (PEO) was immobilized by the Williamson ether synthesis onto halogenated surfaces such as poly(vinylidene chloride), surface-brominated polypropylene, and surface-brominated poly(ethylene terephthalate). PEO (Mw 20,000) was converted to its sodium salt and reacted for various times with the halogen-containing surfaces at 95 degrees C in the melt, or as a solution in 2-methoxyethyl ether. X-ray photon spectroscopy and water contact-angle measurements confirmed the surface-immobilization of PEO. The adsorption from phosphate buffer of human serum albumin, immunoglobulin G (IgG) and fibrinogen, and murine IgG was reduced after modification of the surfaces. In addition, IgG adsorption from pooled human sera was diminished. The difference in protein adsorption between test samples and controls exhibited a strong dependence on input protein concentration.

Adsorption↗

Effect on uropathogens of prophylaxis for urinary tract infection in spinal cord injured patients: preliminary study.

Spinal cord injured patients are highly prone to urinary tract infections. The high frequency of recurrences, the problems with drug resistance and the difficulties associated with diagnosis complicate the management. In a preliminary retrospective study of 30 patient files, we discovered that prophylactic antimicrobial therapy with trimethoprim-sulfamethoxazole, significantly reduced the incidence of symptomatic urinary tract infections. The prevention of infection resulted in cheaper healthcare expenses than treatment. ONe problematic outcome was that antibiotic therapy resulted in a dramatic change in the population of uropathogens infecting the host, from a predominantly Gram negative type to one dominated by Enterococcus faecalis.

Adolescent↗

Clinical outcome of geriatric patients in the United States receiving home parenteral and enteral nutrition.

In this study the use of home parenteral and enteral nutrition (HPEN) therapy in geriatric patients and the effect of aging on the clinical outcome of HPEN therapy was assessed between 1985 and 1992. Data were obtained from Medicare (part B) parenteral and enteral nutrition workload statistics, Blue Cross and Blue Shield of South Carolina, and the North American HPEN Patient Registry. On the basis of these data it was estimated that in 1992 there were 40,000 HPN patients and 152,000 HEN patients nationwide. One-quarter to one-third of the HPN group was aged > or = 65 y, depending on the underlying diagnosis. Geriatric HPN patients had a generally good outcome but did not do as well as their younger counterparts; however, they had fewer therapy-related complications than children. In the HEN group, 44% of cancer patients and 69% of patients with neuromuscular swallowing disorders were geriatric. Geriatric HEN patients with swallowing disorders had a poorer outcome (i.e., lower survival, poorer rehabilitation, and fewer resumed full oral nutrition) than younger patients after 1 y of follow-up. In conclusion, although aging was associated with a poorer outcome for HPN patients, it was still reasonably good; therefore, age per se should not exclude geriatric subjects from therapy. For HEN, the poorer outcome in geriatric dysphagic patients raises concern regarding the appropriateness of this therapy.

Adolescent↗

Making local pay helpful--Part 2: Using action research to address the challenge.

Second part of an item featuring action research with four different trusts to investigate factors relating to the implementation of the local pay policy. Describes methodologies used, such as clinical team diagnosis and cognitive mapping. Looks at the way forward, listing critical factors in ensuring successful implementation.

Efficiency, Organizational↗

Making local pay helpful--Part 1: Surfacing the hidden challenge.

Reports on a project which looked into the impact of "local pay" on four different types of Trust. Notes that all four were working towards ameliorating the perceived threat of local pay. Reports the use of various methodological approaches such as semi-structured interviews and a team diagnostic exercise and comes up with numerous findings.

Efficiency, Organizational↗

The presence of a C1-inhibitor-like molecule (C1-INH-L) on human sperm: its involvement in sperm motility.

PROBLEM: An 88-92-kDa C1-inhibitor-like molecule (C1-INH-L) was previously identified to elicit cytotoxic sperm antibody response in infertile men and women. Here, we document that it is present on the human sperm surface and could be detected by an enzyme-labeled immunoglobulin G (IgG) fraction of anti-human C1-INH antibody. METHOD OF STUDY: Western blot analysis, enzyme-lined immunoadsorbent assay (ELISA) and computerized sperm motion analysis. RESULTS: The existence of C1-INH-L on the sperm surface is calcium independent. Phosphatidylinositol-specific phospholipase C (PIPLC), EDTA, and acid (pH 3.0) could not remove the C1-INH-L from sperm, but trypsin did. Activated C1s was able to bind to the sperm surface. Immunofluorescence studies localized the protein to the head and midpiece of the sperm membrane. The C1-INH-L exists on both uncapacitated and capacitated sperm surfaces, which suggests that this protein is a sperm-surface protein. The heat-treated (56 degrees C, 30 min) IgG fraction of anti-C1-INH greatly reduced the percentage of motile spermatozoa and the progressive and path velocities in the absence of complement. CONCLUSION: Our data suggest that C1-INH is a sperm membrane-anchored protein that may have complement and sperm motility regulatory function.

Complement C1 Inactivator Proteins↗

Impact factors of psychiatric journals.

BACKGROUND: We examined citation data for the British Journal of Psychiatry (BJP) and four other general psychiatry journals to assess their impact on the scientific community. METHOD: Data on three measures of citations (total number of citations, impact factor and ranking by impact factor) were obtained from Journal Citation Reports for 1985-1994. Rank correlations from year to year were calculated. RESULTS: The BJP currently ranks sixth of all psychiatry journals when journals are ranked by impact factor. The journal's impact factor fell between 1985 and 1990 and this was followed by a rise in impact factor after 1991. The BJP did not rank in the top 10 psychiatry journals between 1991 and 1993. Archives of General Psychiatry is cited more frequently than any other psychiatry journal, with the American Journal of Psychiatry usually ranking second. Psychopharmacology journals are replacing more general journals in the top rankings. Rankings of most journals have become less stable in recent years. CONCLUSIONS: The BJP would have to change the nature and number of papers published to improve its impact factor. There are a number of limitations to citation data and such data are only one of several factors useful in evaluating the importance of a journal's contribution to scientific and clinical communities.

Bibliometrics↗