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Biomedical subjects

K Cooper

Publications and source records attributed to K Cooper.

At least 19 recordsLinked to original sources
PubMed2001

Pivotal phase III trial of two dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma.

PURPOSE: The objective of this phase III study was to determine the efficacy, safety, and pharmacokinetics of denileukin diftitox (DAB389IL-2, Ontak [Ligand Pharmaceuticals Inc, San Diego, CA]) in patients with stage Ib to IVa cutaneous T-cell lymphoma (CTCL) who have previously received other therapeutic interventions. PATIENTS AND METHODS: Patients with biopsy-proven CTCL that expressed CD25 on > or = 20% of lymphocytes were assigned to one of two dose levels (9 or 18 microg/kg/d) of denileukin diftitox administered 5 consecutive days every 3 weeks for up to 8 cycles. Patients were monitored for toxicity and clinical efficacy, the latter assessed by changes in disease burden and quality of life measurements. Antibody levels of antidenileukin diftitox and anti-interleukin-2 and serum concentrations of denileukin diftitox were also measured. RESULTS: Overall, 30% of the 71 patients with CTCL treated with denileukin diftitox had an objective response (20% partial response; 10% complete response). The response rate and duration of response based on the time of the first dose of study drug for all responders (median of 6.9 months with a range of 2.7 to more than 46.1 months) were not statistically different between the two doses. Adverse events consisted of flu-like symptoms (fever/chills, nausea/vomiting, and myalgias/arthralgias), acute infusion-related events (hypotension, dyspnea, chest pain, and back pain), and a vascular leak syndrome (hypotension, hypoalbuminemia, edema). In addition, 61% of the patients experienced transient elevations of hepatic transaminase levels with 17% grade 3 or 4. Hypoalbuminemia occurred in 79%, including 15% with grade 3 or 4 changes. Tolerability at 9 and 18 microg/kg/d was similar, and there was no evidence of cumulative toxicity. CONCLUSION: Denileukin diftitox has been shown to be a useful and important agent in the treatment of patients whose CTCL is persistent or recurrent despite other therapeutic interventions.

Adult↗
PubMed2001

Carcinosarcoma of the uterine cervix: a report of eight cases with immunohistochemical analysis and evaluation of human papillomavirus status.

Carcinosarcomas (malignant Müllerian mixed tumors [MMMTs]) of the uterine cervix are rare neoplasms. This report describes the morphology, immunohistochemical profiles, and human papillomavirus (HPV) status of eight cervical MMMTs. Patients' ages ranged from 32 to 93 years (mean, 61 years). Seven cases showed in situ squamous cell carcinoma (SCC). The invasive epithelial component (EC) was composed of combined adenoid basal carcinoma, basaloid SCC, and adenoid cystic carcinoma (ACC) in two cases. Keratinizing SCC, large cell nonkeratinizing SCC, undifferentiated carcinoma, and basaloid SCC predominated in the remaining tumors, one of which had admixed ACC. The sarcomatous component (SC) was homologous and spindled with admixed myxoid areas in three lesions. The ECs and SCs in six MMMTs showed dual immunostaining with epithelial membrane antigen and the pan-keratin marker, MNF116. The SC was vimentin-positive in seven cases. Five tumors had a vimentin-positive EC. The SC was positive for muscle specific actin and/or smooth muscle actin in seven lesions, of which four were desmin-positive. Polymerase chain reaction (PCR) using GP5+/GP6+ L1 consensus primers detected HPV DNA in all eight cases. Nonisotopic in situ hybridization with digoxigenin-labeled probes to HPV types 6, 11, 16, 18, 31 and 33 demonstrated integrated HPV 16 in three cases, not only in the EC, but also in nuclei of the SC. This is the first study to implicate HPV in the evolution of cervical MMMTs. The above observations lend support to a metaplastic theory of histogenesis.

Adult↗
PubMed2001

Chlamydia trachomatis in the endometrium: can surgical pathologists identify plasma cells?

Chlamydia trachomatis infection is the most common bacterial sexually transmitted disease. The authors examined the relation between chronic endometritis, which they term plasma cell endometritis (PCE), and chlamydial infection using plasmid-based polymerase chain reaction (PCR) and immunohistochemical staining (IHC) of paraffin-embedded endometrial sections. C. trachomatis infection was detected in 5 (24%) of 21 cases of PCE and in 1 (4%) of histologically normal endometrium. The diagnosis of chronic endometritis (with plasma cells confirmed by methyl green pyronin staining) was correctly made in 74% of the cases originally diagnosed as PCE and in 23% of control cases originally diagnosed as normal. The authors conclude that the histopathologic finding of plasma cells in endometrial samples should encourage further examination for chlamydial infection.

Adult↗
PubMed2001

Investigation of human papillomavirus in transitional cell carcinomas of the urinary bladder in South Africa.

AIM: To investigate the prevalence of human papillomavirus in transitional cell carcinoma of the urinary bladder in South Africa. METHODS: Ninety-one archival samples of bladder transitional cell carcinoma were subjected to polymerase chain reaction (PCR) and non-isotopic in situ hybridisation (NISH) for the detection of human papillomavirus 6, 11, 16, 18, 31, and 33 genotypes. RESULTS: HPV was detected in only one case with PCR. HPV was not detected in any of the cases subjected to the NISH system. CONCLUSION: This study shows that although HPV has been shown to be associated with uterine cervical and esophageal squamous cell carcinomas in South Africa, this virus is not present in the transitional cell carcinoma of the urinary bladder in this geographical location. It is suggested that other factors, including nitrosamine exposure, p53 mutation, and additional unknown chromosomal events, may play a role in the carcinogenesis of this neoplasm in the bladder.

Beta-Globulins↗
PubMed2001

The natural history of lower urinary tract symptoms in black American men: relationships with aging, prostate size, flow rate and bothersomeness.

PURPOSE: Studies of lower urinary tract symptoms in men have been restricted to predominately white populations and these observations may not be generalized to black American men. A goal of the Flint Men's Health Study was to evaluate the prevalence of lower urinary tract symptoms in a community based sample of black American men. MATERIALS AND METHODS: We identified 721 eligible subjects after a 2-stage stratified sampling protocol of black American men residing in Flint, Michigan and an in-home interview. Of these men 364 (50%) completed the study protocol, including serum prostate specific antigen measurement, digital rectal examination, uroflowmetry and transrectal ultrasound. These men comprised our study group. Patients completed the American Urological Association (AUA) symptom and bothersomeness scores. Moderate to severe symptoms and impairment were defined as an AUA symptom score of greater than 7 and bothersomeness score of greater than 3, respectively. Data were stratified by 10-year age groups. RESULTS: Prostate volume increased, while the peak urinary flow rate decreased with increasing age (p <0.001). Total AUA symptom and bothersomeness scores were marginally associated with age (p = 0.08 and 0.01, respectively). Although only 8.2% of the men reported an enlarged prostate and 3% reported being on medical therapy for benign prostatic hyperplasia, moderate to severe lower urinary tract symptoms were reported by 39.6% and moderate to severe impairment was present in 35%. CONCLUSIONS: To our knowledge this is the first study to describe the prevalence of lower urinary tract symptoms and its associations with age, prostate size and peak flow rate in a black American population. A large proportion of the men in this study had from moderate to severe lower urinary tract symptoms, of whom many were undiagnosed and untreated. The AUA symptom score has the potential to identify these men and its validity in black Americans has now been established.

Adult↗
PubMed2000

Substrate Morphology and Particle Adhesion in Reacting Systems.

This paper describes an effort to measure and model changes in the adhesion of micron-scale particles to substrates in systems in which chemical reactions are occurring. Contact interactions between polystyrene latex spheres and silicon substrates (with surface oxide) immersed in aqueous KNO(3) solutions were studied. Two important results were obtained. First, it was shown that the AFM can be employed to monitor, in situ, changes in adhesive interactions induced by surface chemical reactions in this system. Second, the morphology of the interacting surfaces plays a controlling role in particle adhesion. In particular, for this system, changes in roughness of the substrate changed the interaction force by nearly 90%. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Drosophila dumpy is a gigantic extracellular protein required to maintain tension at epidermal-cuticle attachment sites.

BACKGROUND: Growth and morphogenesis during development depend both on patterning genes, which assign positional information, and on genes that regulate mechanical forces. The dumpy gene of the fruit fly Drosophila melanogaster is an example of the latter class, with mutant phenotypes affecting size and shape of the limbs, thoracic cuticle, trachea and mouthparts. RESULTS: The genetically complex dumpy locus was found to span over 100 kb and encode a gigantic 2.5 MDa extracellular matrix protein. Dumpy represents an extreme form of modular protein evolution, containing 308 epidermal growth factor (EGF) modules, interspersed with a new module class, DPY, and terminating in a crosslinking zona pellucida domain and membrane anchor sequence. We determined the three-dimensional structure of the DPY module by nuclear magnetic resonance (NMR) spectroscopy and found that it forms a disulphide-stabilised beta sheet motif, capable of linking end-to-end with EGF modules to form a fibre. Consistent with its cuticle phenotypes, dumpy is expressed at several sites of cuticle-epidermal cell attachment, including the trachea and the muscle tendon cells, which mediate anchorage of the muscles to the cuticle. CONCLUSIONS: The dumpy gene encodes a gigantic extracellular molecule that we predict to be a membrane-anchored fibre of almost a micrometer in length. Insertion and crosslinking of this fibre within the cuticle may provide a strong anchor for the underlying tissue, allowing it to maintain mechanical tension at sites under stress. This would explain its contribution to tissue morphogenesis through its regulation of mechanical properties.

Amino Acid Sequence↗
PubMed2000

Analysis of Contact Interactions between a Rough Deformable Colloid and a Smooth Substrate.

A model was developed for the effect of van der Waals interactions between a rough, deformable, spherical colloid and a flat, smooth, hard surface in contact. The model demonstrates the significant effect of colloid roughness on removal force. Small changes in colloid roughness produce large changes in the predicted removal force. Several authors attribute discrepancies in the observed interaction force between particles and surfaces to colloid roughness, and our model supports their hypotheses. Experimental data documenting the force required to remove colloids of polystyrene latex from silica substrates in aqueous solution were collected during AFM studies of this system. When colloid roughness exists, as is the case in this work, our model bounds the observed removal force. The predicted range of removal forces is in better quantitative agreement with our removal force data than are forces predicted by classical DLVO theory. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Anterior vaginal repair for urinary incontinence in women.

BACKGROUND: Anterior vaginal repair (anterior colporrhaphy) is an operation traditionally used for moderate or severe stress urinary incontinence in women. About a third of adult women experience urinary incontinence. OBJECTIVES: To determine the effects of anterior vaginal repair (anterior colporrhaphy) on stress or mixed urinary incontinence in comparison with other management options. SEARCH STRATEGY: We searched the Cochrane Incontinence Group's trials register, and the reference lists of relevant articles. Date of most recent search: March 1999. SELECTION CRITERIA: Randomised or quasi-randomised trials that included anterior vaginal repair for the treatment of urinary incontinence. DATA COLLECTION AND ANALYSIS: Both reviewers independently extracted data and assessed trial quality. One trial investigator was contacted for additional information. MAIN RESULTS: Five trials were identified which included 208 women having an anterior vaginal repair and 400 who received comparison interventions. A single small trial provided insufficient evidence to assess anterior repair in comparison with physical therapy. The performance of anterior repair in comparison with needle suspension appeared similar but clinically important differences could not be confidently ruled out. No trials compared anterior repair with sling or laparoscopic interventions, or compared alternative vaginal operations. Anterior repair was less effective than abdominal retropubic suspension based on patient-reported cure rates in four trials both in the short-term (failure rate within first year after anterior repair 48/198, 24% vs 30/266, 11%; RR 2.15, 95% CI 1.4 to 3.28) and long-term (80/193, 41% vs 51/261, 20%; RR 2.25, 95% CI 1.66 to 3.04). There was some evidence from one of these trials that this was reflected in fewer repeat operations for incontinence. These findings held irrespective of the co-existence of prolapse (pelvic relaxation). Although later prolapse operation appeared to be equally common after vaginal or abdominal operation there were too few data to judge this reliably. In respect of the type of abdominal retropubic suspension, most data related to comparisons of anterior repair with Burch colposuspension. The few data describing comparison of anterior repair with the Marshall-Marchetti-Krantz procedure were consistent with those for Burch colposuspension. REVIEWER'S CONCLUSIONS: There were not enough data to allow comparison of anterior vaginal repair with physical therapy or needle suspension for primary urinary stress incontinence in women. Abdominal retropubic suspension appeared to be better than anterior vaginal repair judged on subjective cure rates in four trials, even in women who had prolapse in addition to stress incontinence. The need for repeat incontinence surgery also appeared less after the abdominal operation, but this was only reported in one small trial. However, there was not enough information about post-operative complications and morbidity.

Adult↗
PubMed2000

A generalized fecal glucocorticoid assay for use in a diverse array of nondomestic mammalian and avian species.

Noninvasive fecal glucocorticoid analysis has tremendous potential as a means of assessing stress associated with environmental disturbance in wildlife. However, interspecific variation in excreted glucocorticoid metabolites requires careful selection of the antibody used in their quantification. We compared four antibodies for detecting the major fecal cortisol metabolites in yellow baboons following (3)H cortisol administration, ACTH challenge, and HPLC separation of fecal glucocorticoid metabolites. The most effective antibody (ICN corticosterone RIA; Cat. No. 07-120102) demonstrated relatively high cross-reactivities to the major cortisol metabolites present in feces during peak excretion, following both radiolabel infusion and ACTH challenge. This same antibody also detected increased fecal glucocorticoid metabolites after ACTH administration in the African elephant, black rhinoceros, Roosevelt elk, gerenuk, scimitar-horned oryx, Alaskan sea otter, Malayan sun bear, cheetah, clouded leopard, longtailed macaque, and northern spotted owl. Results suggest that (1) fecal glucocorticoid assays reliably detect endogenous changes in adrenal activity of a diverse array of species and (2) where comparisons were made, the ICN corticosterone antibody generally was superior to other antibodies for measuring glucocorticoid metabolites in feces.

Adrenocorticotropic Hormone↗
PubMed2000

IgA nephropathy, the most common cause of glomerulonephritis, is linked to 6q22-23.

End-stage renal disease (ESRD) is a major public health problem, affecting 1 in 1,000 individuals and with an annual death rate of 20% despite dialysis treatment. IgA nephropathy (IgAN) is the most common form of glomerulonephritis, a principal cause of ESRD worldwide; it affects up to 1.3% of the population and its pathogenesis is unknown. Kidneys of people with IgAN show deposits of IgA-containing immune complexes with proliferation of the glomerular mesangium (Fig. 1). Typical clinical features include onset before age 40 with haematuria and proteinuria (blood and protein in the urine), and episodes of gross haematuria following mucosal infections are common; 30% of patients develop progressive renal failure. Although not generally considered a hereditary disease, striking ethnic variation in prevalence and familial clustering, along with subclinical renal abnormalities among relatives of IgAN cases, have suggested a heretofore undefined genetic component. By genome-wide analysis of linkage in 30 multiplex IgAN kindreds, we demonstrate linkage of IgAN to 6q22-23 under a dominant model of transmission with incomplete penetrance, with a lod score of 5.6 and 60% of kindreds linked. These findings for the first time indicate the existence of a locus with large effect on development of IgAN and identify the chromosomal location of this disease gene.

Chromosome Mapping↗
PubMed2000

A randomised controlled trial to compare the effectiveness of ice-packs and Epifoam with cooling maternity gel pads at alleviating postnatal perineal trauma.

OBJECTIVE: To evaluate the effectiveness of standard regimes (ice packs and Epifoam) at relieving perineal trauma and compare these with a new cooling device (maternity gel pad). DESIGN: A randomised controlled trial involving three treatment groups. The women were free to choose the time of initial application (within four hours after delivery) in all treatment groups and the number of subsequent treatments up to 48 hours after suturing. SETTING: A midwifery unit in the north of England and then continued in the women's own homes. PARTICIPANTS: 120 women who had undergone an instrumental delivery and had a 48 hours post-delivery stay in a postnatal ward. MEASUREMENTS AND FINDINGS: The ordinal scale of none, mild, moderate and severe was used to determine the levels of perineal oedema and bruising at initial assessment (less than 4 hours), 24 hours and at 48 hours, by use of a newly developed visual evaluating tool. Self-assessed pain was recorded using a 10-point visual analogue scale within four hours, at 24 hours, 48 hours, and finally at five days after suturing. Women's opinions as to the effectiveness of their treatment was rated by use of a 5-point scale describing the categories; poor, fair, good, very good and excellent. A high proportion of women had some perineal oedema at initial assessment. A statistically significant difference in the proportion of women with oedema was found between treatment groups at 48 hours (p = 0.01), which was in favour of the maternity gel pad group. This was particularly noticeable for women with initial levels of mild oedema (p = 0.017). Localised treatment with the gel pad caused a significant decrease in reported pain at 48 hours in women who initially demonstrated moderate or severe pain (p = 0.048). A significant increase in the proportion of women with some bruising was seen across all treatment groups from initial assessment, through 24 hours to 48 hours (p < 0.0005). The bruising was significantly less in the gel-pad group in women who initially had no bruising (p = 0.021). There was no statistically significant effect of treatment at other initial levels of severity for oedema, bruising or pain at 24 hours, 48 hours and five days (for pain). Women in the gel-pad group rated the effectiveness of their localised treatment to be significantly higher than women in the other two treatment groups (p < 0.0005). KEY CONCLUSIONS: This trial demonstrated that a high proportion of women experience perineal oedema, bruising and pain following an instrumental delivery, which continues for at least five days for perineal pain, despite oral analgesia. Maternity gel pads, which were specially designed to cool the perineal region, were more effective in alleviating perineal trauma when compared with hospital standard regimens and were more highly rated by women.

Adult↗