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Biomedical subjects

S Kane

Publications and source records attributed to S Kane.

At least 19 recordsLinked to original sources

Adherence rates with infliximab therapy in Crohn's disease.

BACKGROUND: Inflammatory bowel disease is associated with non-adherence to treatment with oral medications. AIM: To assess the intravenous infliximab adherence rate and identify risk factors for non-adherence to treatment. METHODS: Infliximab infusion dates for 1 June 2002-30 October 2003 were obtained. Additional information was obtained from two other administrative and patient-based databases. Non-adherence was defined as a 'No Show' designation for a scheduled appointment. Non-adherence rate, odds ratios for associations to 'No Show' appointments and analysis were performed to identify patient characteristics associated with non-adherent behaviour. RESULTS: One thousand hundred and eighty-five infliximab infusions were scheduled for 274 patients. Forty-eight (4%) of appointments were classified as 'No Show'. Six patients accounted for 13/48 (27%) of failed appointments; another 35 patients missed one appointment. 'No Show' appointments were more likely to be for female patients, those on concomitant immunomodulators and those >18 weeks from initial infusion. Patients who missed >1 appointment were more likely to be female and have Medicaid vs. those with only one missed appointment (P < 0.05). Indication, patient area code and race were not significantly associated with single or repeated No Show behaviour. CONCLUSIONS: Overall, the non-adherence rate for infliximab is low. Risk factors that may contribute to non-adherence to treatment include female gender and maintenance dosing.

Adolescent↗

Biochemical effects of two different hyaluronic acid products in a co-culture model of osteoarthritis.

OBJECTIVES: To compare the effects of two hyaluronic acid (HA) formulations on mediators of matrix turnover and inflammation in an IL-1-treated cartilage-synovium co-culture model with the aim of elucidating mechanisms by which viscosupplementation exerts beneficial effects in osteoarthritic joints. DESIGN: A co-culture model (100 ng/ml interleukin-1beta (IL-1beta) added to canine synovial and cartilage explants) was used to investigate the effects of HA on cartilage-synovium interactions. Three concentrations (1x, 0.5x, and 0.1x) of two commercial sources of HA (A: Synvisc [hylan G-F 20]; B: Hyalgan [sodium hyaluronate]) were used. Co-cultures without IL-1beta (negative) or with IL-1beta (positive) but neither HA product served as controls. The liquid media were collected every 3 days and explants of cartilage and synovium were collected on days 3, 6, and 20. Media and explants were analyzed histologically, biochemically, and immunohistochemically. RESULTS: Glycosaminoglycan (GAG) content was measured in cartilage explants. GAG content in explants was higher in both HA groups at the beginning and the conclusion of the study compared to the IL-1beta-treated group. GAG content of the media was significantly (P<0.05) lower in the Synvisc group than all other groups early. The Hyalgan group demonstrated progressively less GAG release later in the study. The addition of Synvisc did not decrease the matrix metalloproteinase (MMP)-3 concentrations at any point. MMP-3 concentrations were significantly (P<0.05) lower among the 1x and 0.5x Hyalgan groups on day 20 compared to the IL-1beta-treated group. On day 3, prostaglandin E(2) concentrations were significantly (P<0.05) higher in the IL-1beta-treated group compared to other groups. Both HA groups had less nitric oxide production than the control groups throughout the study. CONCLUSIONS: This study supports two potential mechanisms for viscosupplementation: a biosynthetic-chondroprotective mechanism, with a possible delay in onset depending on the form of HA; and an anti-inflammatory mechanism.

Animals↗

Discovery of a cool planet of 5.5 Earth masses through gravitational microlensing.

In the favoured core-accretion model of formation of planetary systems, solid planetesimals accumulate to build up planetary cores, which then accrete nebular gas if they are sufficiently massive. Around M-dwarf stars (the most common stars in our Galaxy), this model favours the formation of Earth-mass (M(o)) to Neptune-mass planets with orbital radii of 1 to 10 astronomical units (au), which is consistent with the small number of gas giant planets known to orbit M-dwarf host stars. More than 170 extrasolar planets have been discovered with a wide range of masses and orbital periods, but planets of Neptune's mass or less have not hitherto been detected at separations of more than 0.15 au from normal stars. Here we report the discovery of a 5.5(+5.5)(-2.7) M(o) planetary companion at a separation of 2.6+1.5-0.6 au from a 0.22+0.21-0.11 M(o) M-dwarf star, where M(o) refers to a solar mass. (We propose to name it OGLE-2005-BLG-390Lb, indicating a planetary mass companion to the lens star of the microlensing event.) The mass is lower than that of GJ876d (ref. 5), although the error bars overlap. Our detection suggests that such cool, sub-Neptune-mass planets may be more common than gas giant planets, as predicted by the core accretion theory.

Journal Article↗

Concurrent evaluation of visual, cytological and HPV testing as screening methods for the early detection of cervical neoplasia in Mumbai, India.

OBJECTIVE: Naked eye visual inspection with acetic acid (VIA), magnified VIA (VIAM), visual inspection with Lugol's iodine (VILI), cytology and human papillomavirus (HPV) testing were evaluated as screening methods for the detection of high-grade squamous intraepithelial lesions (HSIL) of the uterine cervix in a cross-sectional study in Mumbai, India. METHODS: Cytology, HPV testing, VIA, VIAM and VILI were carried out concurrently for 4039 women aged 30-65 years. All women were investigated with colposcopy and biopsies were taken from 939 women who had colposcopic abnormalities. The reference standard for final disease status was histology or negative colposcopy. The presence of HSIL was confirmed in 57 women (1.4%). The test characteristics for each method were calculated using standard formulae. RESULTS: The sensitivities of cytology, HPV testing, VIA, VIAM and VILI were 57.4%, 62.0%, 59.7%, 64.9%, and 75.4%, respectively (differences were not statistically significant). The specificities were 98.6%, 93.5%, 88.4%, 86.3%, and 84.3%, respectively. Adding a visual test to cytology or HPV testing in parallel combination resulted in a substantial increase in sensitivity, with a moderate decrease in specificity. The parallel combination of VILI and HPV testing resulted in a sensitivity of 92.0% and a specificity of 79.9%. CONCLUSION: As a single test, cytology had the best balance of sensitivity and specificity. Visual tests are promising in low-resource settings, such as India. The use of both VIA and VILI may be considered where good quality cytology or HPV testing are not feasible. The sensitivity of cytology and HPV testing increased significantly when combined with VIA or VILI.

Adult↗

Intentional infliximab use during pregnancy for induction or maintenance of remission in Crohn's disease.

AIM: To study the effects of infliximab on pregnancy and foetal outcome. METHODS: We conducted a retrospective chart review of women with Crohn's disease treated intentionally with infliximab during pregnancy. The primary outcome measure was the occurrence of congenital malformations. Secondary outcome measures were the rate of premature birth, low-birth weight, small for gestational age infants, intrauterine growth retardation and caesarean section. RESULTS: Ten women were identified. Eight women received maintenance infliximab infusions throughout their pregnancy and two women received their initial infliximab infusions during pregnancy. All 10 pregnancies ended in live births. No infants had congenital malformations, intrauterine growth retardation or small for gestational age parameters. Three infants were premature and one had low-birth weight. Eight women had a caesarean section. CONCLUSIONS: This is the first reported series of intentional infliximab use throughout pregnancy. These data, combined with other studies of inadvertent use of infliximab during pregnancy, suggest that the benefits of infliximab in achieving response and maintaining remission in mothers with Crohn's disease may outweigh the risk to the foetus of exposure to the drug. Further prospective data collection will be helpful to confirm these findings.

Abnormalities, Drug-Induced↗

The RadB protein from Pyrococcus does not complement E. coli recA mutations in vivo.

A previous publication claimed that the radB gene called Pk-REC from Pyrococcus furiosus complemented an E. coli recA mutation. We found that a sequencing error had led to the test of a mutant form of Pk-REC. The wild-type radB gene from P. furiosus cloned in a similar expression vector to the mutant Pk-REC also appeared to complement an E. coli recA mutation. However, the cloned P. furiosus gdh (glutamate dehydrogenase) gene showed the same activity. We therefore concluded that overexpression of any protein can produce an artificial growth inhibition or stationary phase in recA mutant cells, which allows cells to recover from UV damage due to the action of repair systems that do not require RecA-like activity.

Amino Acid Sequence↗

Cluster and regional influences on suicide in a Southwestern American Indian tribe.

Suicide is the second leading cause of death among American Indian youth. Elevated rates of suicide in Indian communities have been attributed both to outbreaks and to regional trends. We assessed the contribution of these two factors for a single tribe, and attempted to define a profile of individuals at risk. Data came from the tribe's registry of suicide attempts and completions for 1990-1993 and analysis of death certificates for the period 1985-1996. Using combined tribal and death certificate data, the average annual (age-adjusted) rate of completed suicide among tribal members was 44.7/100,000 for 1990-1993. Within the 45 suicide deaths and serious attempts in this time period, we identified one grouping of seven cases taking place in a 40-day period. All seven involved hanging and youth (13-28 years old). Using death certificate data alone, the average annual rate of suicide death for non-natives in the surrounding county in the period 1985-1996 was 22.7/100,000. Age-adjusted to the county population, the tribal rate for the same period was not significantly different (24.6/100,000). Tribal and county suicide patterns differed by age distribution and method but not by gender. We concluded that both regional trends and clustering contribute to suicide in this community. Further prevention efforts may need to focus on both unique tribal characteristics and shared factors among non-native neighbors.

Adolescent↗

The synaptic vesicle protein, cysteine-string protein, is associated with the plasma membrane in 3T3-L1 adipocytes and interacts with syntaxin 4.

Adipocytes and muscle cells play a major role in blood glucose homeostasis. This is dependent upon the expression of Glut4, an insulin-responsive facilitative glucose transporter. Glut4 is localised to specialised intracellular vesicles that fuse with the plasma membrane in response to insulin stimulation. The insulin-induced translocation of Glut4 to the cell surface is essential for the maintenance of optimal blood glucose levels, and defects in this system are associated with insulin resistance and type II diabetes. Therefore, a major focus of recent research has been to identify and characterise proteins that regulate Glut4 translocation. Cysteine-string protein (Csp) is a secretory vesicle protein that functions in presynaptic neurotransmission and also in regulated exocytosis from non-neuronal cells. We show that Csp1 is expressed in 3T3-L1 adipocytes and that cellular levels of this protein are increased following cell differentiation. Combined fractionation and immunofluorescence analyses reveal that Csp1 is not a component of intracellular Glut4-storage vesicles (GSVs), but is associated with the adipocyte plasma membrane. This association is stable, and not affected by either insulin stimulation or chemical depalmitoylation of Csp1. We also demonstrate that Csp1 interacts with the t-SNARE syntaxin 4. As syntaxin 4 is an important mediator of insulin-stimulated GSV fusion with the plasma membrane, this suggests that Csp1 may play a regulatory role in this process. Syntaxin 4 interacts specifically with Csp1, but not with Csp2. In contrast, syntaxin 1A binds to both Csp isoforms, and actually exhibits a higher affinity for the Csp2 protein. The results described raise a number of interesting questions concerning the intracellular targeting of Csp in different cell types, and suggest that the composition and synthesis of GSVs may be different from synaptic and other secretory vesicles. In addition, the interaction of Csp1 with syntaxin 4 suggests that this Csp isoform may play a role in insulin-stimulated fusion of GSVs with the plasma membrane.

3T3 Cells↗

Caring for women with inflammatory bowel disease.

Crohn's disease and ulcerative colitis are chronic inflammatory conditions involving the gastrointestinal tract. Although many aspects of the management of these diseases are identical for all patients, some issues that are specific to women are not necessarily part of routine care. Gender-specific issues such as menses, fertility, pregnancy, and menopause are often overlooked and mismanaged. Women and men also have different psychological concerns arising from the disease. Health care providers, regardless of their primary focus, should be aware of these differences and should be familiar with certain general information on gender-specific issues, reviewed in this article.

Body Image↗

Nerve cell markers in ossifying fibromyxoid tumour of soft parts.

Reported herein are two benign ossifying fibromyxoid tumors (OFMTs) of the soft tissues in axilla and terminal phalanx respectively. Both cases on immunohistochemistry (IHC) showed reactivity for vimentin, S-100 protein and glial fibrillary acidic protein (GFAP) antibodies. In addition, a focal/diffuse strong positivity for neurofilament (NF) and neuron specific enolase (NSE) was observed. Electron microscopy in one instance revealed abundant intermediate filaments, primitive cell junctions and a focally present external lamina. In the light of nerve cell differentiation of these tumors and the similarity of IHC profile and EM features of OFMT to a poorly differentiated malignant peripheral nerve sheath tumor (MPNST); it is suggested that OFMT is a variably differentiated PNST rather than a simple Schwannian neoplasm as is believed.

Adult↗

Mullerian adenosarcoma of the uterine cervix.

Sarcomas in the uterine cervix are rare, the incidence being 0.5% to 1% of all cervical malignancies. This is a report of cervical mullerian adenosarcoma, which was encountered in a hysterectomy performed for prolapse. The tumor was composed of benign glandular elements and malignant stromal component, thus justifying its nomenclature. We wish to emphasize the distinctive morphological features of this rare cervical tumor.

Adenosarcoma↗

Histoplasmosis capsulatum as a cause of lower gastrointestinal bleeding in common variable immunodeficiency.

Infection with Histoplasma capsulatum is the most common systemic fungal infection in the United States, but symptomatic gastrointestinal disease is rare. Gastrointestinal involvement is seen in patients with an established immunosuppressed state that predates any infection. We report a patient presenting with gastrointestinal bleeding ultimately diagnosed with disseminated histoplasmosis. Work-up led to the diagnosis of common variable immunodeficiency, a diagnosis not previously described as associated with gastrointestinal histoplasmosis. Resolution of the colonic ulcer was documented after appropriate antifungal therapy, underscoring the importance of including this infectious process in the differential of a patient without other risk factors for colonic ulceration.

Common Variable Immunodeficiency↗