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Biomedical subjects

S Hyde

Publications and source records attributed to S Hyde.

At least 19 recordsLinked to original sources

Welfare dental intervention improves employment and quality of life.

Chronic, untreated oral disease adversely affects one's systemic health, quality of life, and economic productivity. This study evaluated the effect of rehabilitative dental treatment on the oral-health-related quality of life and employment of welfare recipients. Three hundred and seventy-seven participants in a novel welfare dental program received oral examinations, questionnaires, and rehabilitative dental treatment. Seventy-nine percent of participants exhibited improvement in their oral-health-related quality-of-life scores following dental treatment. Improved OHIP-14 change scores were associated with being Caucasian or African-American, initial poor general health, severity of treatment urgency, worse baseline oral-health-related quality-of-life scores, subsequent patient satisfaction with the Dental Program, and resolution of their chief complaint (all p < 0.04). Those who completed their dental treatment were twice as likely to achieve a favorable/neutral employment outcome (OR = 2.01, 95%CI = 1.12, 3.62). Thus, oral health improved the quality of life and employment outcome for this welfare population.

Adult↗

Validity of the EK scale: a functional assessment of non-ambulatory individuals with Duchenne muscular dystrophy or spinal muscular atrophy.

BACKGROUND AND PURPOSE: The EK scale comprises ten categories (EK 1-10), each contributing to an overall picture of function in the non-ambulatory stage of Duchenne muscular dystrophy (DMD). The purpose of the present study was to investigate content and construct validity of the EK scale as a tool to discriminate between levels of functional ability in individuals with DMD or spinal muscular atrophy (SMA) who were non-ambulatory. METHOD: Data from a sample of 56 subjects with DMD and 38 with SMA, who were non-ambulatory, were obtained from four separate studies. The relationship of functional ability by use of the EK scale and (1) muscle strength, (2) contractures, (3) forced vital capacity and (4) years of wheelchair dependency were assessed. All items of the EK scale were used except the one representing severe hypoventilation. RESULTS: Regression analyses showed that the EK sum was the most significant explanatory variable (p < 0.05) of all variables measured to explain muscle strength in both DMD and SMA subjects. The individual categories of EK (1-10) all contributed as significant explanatory variables (p < 0.05) to the other variables measured. CONCLUSIONS: The categories and items of the EK scale were relevant and valid as means of discriminating between levels of functional performance in the population studied which was evidence of content and construct validity.

Activities of Daily Living↗

Sarcoma in association with multimodality management of vulvar cancer: two case reports.

BACKGROUND: Radiation-induced or -associated sarcoma is a rare event which has been well described in the literature. However, this entity has been infrequently described in association with genital tract malignancies. To our knowledge it has never been described in association with the management of vulvar cancer. CASES: . Two different cases of sarcoma developing after primary management for vulvar cancer are presented, the first being a case of angiosarcoma developing in the lower abdominal wall 36 months after initial therapy and the second a case of fibrosarcoma developing on the vulva 7 years after multimodality treatment. CONCLUSION: Radiation-associated sarcoma after treatment for vulvar carcinoma is a rare event. A multimodality treatment of carcinoma of the vulva should not be withheld because of fear of sarcomagenesis.

Abdominal Neoplasms↗

Priorities for adult cancer nursing research: a West Australian replication.

Two Delphi surveys have been conducted during the past 20 years to identify cancer nursing research priorities; one in the United States and one in Canada. Sir Charles Gairdner Hospital, the State Cancer Referral Centre in Western Australia, undertook a replication of this Delphi survey to identify nursing research priorities for adult cancer nursing. The aim of this replication was to identify possible changes in priorities and account for cultural difference in the healthcare systems. A total of 45 responses were received from the first Delphi round and 30 from the second. The top ten priorities identified by this sample were different from those identified in prior studies. The top ranked research topic was "What strategies would be most helpful in allowing nurses time to provide emotional support to cancer patients and carers?" These results may stimulate discussion and re-assessment of research priorities in other adult cancer care settings.

Adult↗

Validation of self-reported complications by bone marrow transplantation survivors.

Self-administered questionnaires are commonly used to measure exposures and outcomes in epidemiological research and thus need good validity. With increasing numbers of cancer survivors, there is interest in the ongoing assessment of therapy-related complications. A medical record validation of patient-reported complications following bone marrow transplantation (BMT) was performed using a self-administered questionnaire. The study population consisted of 100 patients who had undergone BMT at the City of Hope. The following self-reported complications were validated using medical records: ocular, endocrine, cardiovascular, musculoskeletal, pulmonary, gastrointestinal, neurological, graft-versus-host disease, and subsequent cancers. Using information from medical records as the standard, sensitivities ranged from 52.9% for subsequent cancers to 100% for avascular necrosis and hypothyroidism. Specificities ranged from 75.4% for ocular complications to 100% for avascular necrosis. There was intermediate to excellent agreement (kappa = 0. 4-1.0) for all complications evaluated. Thus, the agreement between self-reporting and medical records was good for complications with clear diagnostic criteria that are easily communicated to the patient, but was diminished for complications with non-established diagnostic criteria (xerophthalmia) or a fluctuating course (peripheral neuropathies and hypertension). Overall these results suggest that cancer survivors can self-report serious complications with an acceptable level of accuracy in epidemiological research.

Adult↗

Effect of Clostridium difficile toxin A on human colonic lamina propria cells: early loss of macrophages followed by T-cell apoptosis.

We have previously shown that Clostridium difficile toxin A induces detachment of human colonic epithelial cells from the basement membrane and subsequent cell death by apoptosis. Because these cells require adhesion-dependent signalling from the extracellular matrix for survival, their detachment from the basement membrane by other means also induces apoptosis. The role of toxin A in the induction of apoptosis therefore remains to be determined. In addition, sensitivities to C. difficile toxin A of lamina propria lymphocytes, macrophages, and eosinophils, which lie below the surface epithelium, are not known. In contrast to epithelial cells, these lamina propria cells do not require adhesion-dependent signalling from the extracellular matrix for survival, and this may allow the mechanisms of toxin A-induced cell death to be further investigated. The aim of this study was to investigate the effect of purified C. difficile toxin A on human colonic lamina propria T cells, macrophages, and eosinophils. We show that C. difficile toxin A induces loss of viability in isolated colonic lamina propria cell preparations containing the three different cell types in a dose- and time-dependent fashion. Exposure to high concentrations of the toxin led to loss of macrophages within 72 h. T-lymphocyte and eosinophil cell death was prominent at later time points and occurred by apoptosis. Exposure to toxin A also induced the production of tumor necrosis factor alpha by the isolated colonic lamina propria cells. However, the presence of neutralizing antibodies to this cytokine did not influence C. difficile toxin A-induced T-cell apoptosis. Moreover, purified T cells also underwent apoptosis following exposure to toxin A, implying that apoptosis occurred as a consequence of a direct interaction between T cells and the toxin. Our studies suggest that C. difficile toxin A is capable of suppressing human colonic mucosal immune responses by inducing early loss of macrophages followed by T-cell apoptosis.

Apoptosis↗

Clostridium difficile toxin A binding to human intestinal epithelial cells.

Clostridium difficile radiolabelled toxin A ([3H]-toxin A) bound to human duodenal and colonic epithelial cells isolated from endoscopic biopsies. Binding was greater at 4 degrees C than 37 degrees C, consistent with the thermal binding characteristic of toxin A to a carbohydrate moiety. At 37 degrees C colonic cells bound significantly more [3H]-toxin A than duodenal cells. The amount of [3H]-toxin A binding varied considerably between individuals. [3H]-toxin A was displaced by unlabelled toxin A by 50% for duodenal cells and 70% for colonic cells with 94.3 nM unlabelled toxin A. Low non-displacable binding was observed in some samples at 4 degrees C and 37 degrees C, suggesting that these cells came from individuals incapable of specifically binding toxin. Pre-treating cells with alpha- or beta-galactosidases to cleave terminal alpha- and beta-galactose residues reduced [3H]-toxin A binding. There was also a reduction in [3H]-toxin A binding after heat treating cells, which is suggestive of protein binding. The reduction in binding varied between individuals. The reduction of [3H]-toxin A binding, after the removal of beta-linked galactose units, implicates these as components of the receptor and adds credence to the idea that the Lewis X, Y and I antigens may be involved in toxin A binding to human intestinal epithelial cells. However, because the Lewis antigens do not possess terminal alpha-galactose units, the reduction in binding after alpha-galactosidase treatment suggests that other receptors may be involved in toxin A binding to some human intestinal cells. These data are the first demonstration of direct toxin A binding to human intestinal epithelial cells.

Bacterial Toxins↗

Effect of Clostridium difficile toxin A on human intestinal epithelial cells: induction of interleukin 8 production and apoptosis after cell detachment.

Clostridium difficile is the aetiological agent of pseudomembranous colitis, and animal studies suggest the essential role of secreted toxin A in inducing disease. This study examined the biological responses to toxin A by human intestinal epithelial cells. Confluent monolayers of Caco2, HT29, and T84 cells and primary epithelial cells in organ cultures of human colonic biopsy specimens and after detachment with EDTA were studied. Interleukin 8 was assayed using enzyme linked immunosorbent assay (ELISA). Purified C difficile toxin A induced cell rounding and detachment of monolayers of the epithelial cell lines. Cells in detached monolayers initially remained viable while adherent to each other. Subsequently, an increasing number of apoptotic cells appeared in suspension. Exposure to toxin A for 24 hours induced interleukin 8 production in T84 and HT29 cells. Toxin A also induced epithelial cell rounding, detachment, and apoptosis in organ cultures of human colonic biopsy specimens. During culture (in medium only), EDTA detached colonic epithelial cells produced interleukin 8 and cell death occurred by apoptosis. Colonic disease by C difficile may be initiated by toxin A mediated induction of epithelial cell interleukin 8 production and apoptosis after cell detachment from the basement membrane. Studies on isolated (toxin untreated) colonic epithelial cells suggest that interleukin 8 production and apoptosis occur as a consequence of cell injury and detachment.

Apoptosis↗

In vitro model of human umbilical venous perfusion to study the effects of meconium staining of the umbilical cord.

Because meconium diffuses into placental and umbilical cord tissue, its bioactive components are potentially capable of entering the fetal circulation. Meconium diluted in Krebs solution produces vasoconstriction in human umbilical vein segments that are suspended in a milieu similar to that of the amniotic cavity. Based on published observations, we wanted to determine if very diluted meconium could induce vasospasm in intact umbilical cords. Human umbilical cords were obtained from full-term deliveries, cut into 2 equal segments, cannulated, and perfused continuously as test and control cords. The study included four parts: (1) intraluminal meconium (n = 6; 0.01-1% solution); (2) 4-hour exposure to 10% meconium-stained amniotic fluid of intact umbilical cords (n = 8); (3) 4-hour exposure to a 10% meconium-stained amniotic fluid of umbilical cords denuded of their epithelial layer (n = 5); (4) 24-hour exposure to a 10% meconium-stained amniotic fluid of intact umbilical cords (n = 9). Significant vasoconstriction of the umbilical vein occurred only with the intraluminal meconium solution exposure (p = 0.034). In this in vitro model meconium staining of the umbilical cord was not associated with vasoconstriction of the umbilical vein.

Humans↗

Immune responses in humans and animals to meningococcal transferrin-binding proteins: implications for vaccine design.

The results reported here show that the two meningococcal transferrin-binding proteins (TBP1 and TBP2) generate different immune responses in different host species and that there is variation in response dependent on the method of antigen preparation and possibly the route of administration. Mice immunized with either whole cells of Neisseria meningitidis SD (B:15:P1.16) or the isolated TBP1-TBP2 complex from the same strain produced antisera which, when tested against a representative panel of meningococcal isolates by Western blotting (immunoblotting), recognized some but not all heterologous TBP2 molecules. In contrast, rabbit antisera raised to the same preparations were cross-reactive with almost all the TBP2 molecules. The immune response to TBP1 was also host species dependent. Western blot analysis with denatured TBP1 failed to detect antibodies in antisera raised in mice to whole cells or in a rabbit to the TBP1-TBP2 complex but detected broadly cross-reactive antibodies in mouse anti-TBP1-TBP2 complex sera and strain-specific antibodies in rabbit anti-whole-cell serum. Human convalescent-phase sera obtained from five patients infected with meningococci of different serogroups and serotypes contained fully cross-reactive antibodies to TBP2 but no anti-TBP1 antibodies, when examined on Western blots. However, on dot immunoblots, the same patients' sera, as well as the mouse anti-whole cell and the rabbit anti-TBP1-TBP2 complex sera, reacted with purified biologically active TBP1 of strain SD. This indicates that native TBP1, a protein which loses its biological and some of its immunological activities when denatured, is immunogenic and that humans generate cross-reactive antibodies to native epitopes. These observations have important implications for assessing the vaccine potential of TBPs and other meningococcal antigens. Conclusions regarding the usefulness of TBPs as candidate components of meningococcal serogroup B vaccines based on results from certain animal species such as mice, or on methods such as Western blotting, may have little bearing on the situation in humans and may lead to some potentially useful antigens being disregarded.

Animals↗

Translocation (8;13) and T-cell lymphoma. A case report.

A patient with a myeloproliferative disorder is described with an eosinophilia together with T-cell lymphoma. A unique translocation t(8;13)(p11.2;q12) was present in all bone marrow cells examined at presentation. No evidence of this translocation was found in a peripheral blood lymphocyte culture. Chromosome analysis after 9 months revealed this same translocation as well as an extra chromosome 21 in all cells; 4.5% of cells also had an additional chromosome 9. The morphologic diagnosis at this stage was chronic myelomonocytic leukemia. Immunophenotyping 3 months later was consistent with a stem-cell leukemia.

Bone Marrow↗

Evaluation of a commercial enzyme immunoassay kit for the detection of Clostridium difficile toxin A.

A new enzyme immunoassay (EIA) kit developed for the rapid detection of Clostridium difficile toxin A in faecal specimens, Premier (Meridian Diagnostics), was evaluated using 101 faecal specimens. Sixty-nine specimens were positive for Clostridium difficile by isolation of the organism and by cytotoxicity in tissue culture. The EIA for toxin A was positive in 49 of these 69 cases. No specimen that was negative for cytotoxicity was positive by EIA. Eight of the 32 specimens negative by both EIA and cytotoxicity assay yielded Clostridium difficile by culture. In five of these cases the cytotoxigenic status of the isolate was determined, and four were positive. There was no direct relationship between cytotoxin titre and EIA reading.

Animals↗

Molecular, immunological, and biological characterization of a toxin A-negative, toxin B-positive strain of Clostridium difficile.

A cytotoxigenic Clostridium difficile strain that fails to produce toxin A but causes hemorrhage and bloody fluid accumulation in ligated ileal loops of rabbits and hemorrhage and diarrhea in hamsters is described. The lack of reaction of DNA from this strain in hybridization studies with a toxin A gene-specific 4.5-kb probe and polymerase chain reaction studies with six toxin A-specific primers indicate the absence of the toxin A gene. The cytotoxin produced by this strain was not responsible for the enterotoxic or hemorrhagic activity and shared characteristics with toxin B, i.e., its cytotoxicity was neutralized by antibodies to toxigenic strains of C. difficile and Clostridium sordellii. Polymerase chain reaction studies with toxin B-specific primers showed that the DNA from this strain produced a 690-bp product in addition to the expected 591-bp product.

Animals↗

The AIDS epidemic in New York State.

New York State has reported more AIDS cases (26,576) through November 1989 than any other state, accounting for 23 percent of all reported cases in the nation at the time. New York City has reported 22,231 (84 percent) of the statewide cases. The epidemiology of AIDS in New York State has been easily influenced by the large number of cases among IVDUs. Whereas intravenous drug use accounts for 16 percent of adult/adolescent cases in the rest of the nation, it accounts for 39 percent of the cases in New York State. Intravenous drug use is the leading exposure category among racial minorities, with a disproportionately high rate of cases among Blacks and Hispanics. The epidemic among women and children has also been severe, resulting from intravenous drug use by women, heterosexual transmission from drug users to women, and perinatal transmission to their children.

Acquired Immunodeficiency Syndrome↗

A model of bacterially induced umbilical vein spasm, relevant to fetal hypoperfusion.

From experience with placental pathology and autopsies, we hypothesize that infected amniotic fluid may produce umbilical cord and placental surface vasospasm, reduced fetal perfusion, and perinatal asphyxia, morbidity, and mortality. We tested the hypothesis by a preliminary investigation with group B beta-hemolytic streptococcus, a common cause of perinatal morbidity and mortality. Our methods included suspension of isolated human umbilical vein segments in a 30-mL organ bath with modified Krebs solution, pH 7.3-7.4, under continuous aeration by 95% O2 and 5% CO2 at 37C. The vessels were attached to an isometric transducer which was connected to a polygraph. We tested Krebs solution, sterile culture medium, group B streptococcus spent medium, and washed whole group B streptococcus bacteria. Contractility was compared with results produced by 10(-5) M serotonin. The average contraction produced by 30 microL/mL group B streptococcus spent medium was 40.8% of that produced by serotonin. Whole washed bacteria produced 8.6% of the serotonin contraction. Krebs solution and sterile culture medium did not stimulate vascular contraction. Intraperitoneal injection of group B streptococcus spent medium in mice at four times the maximal experimental dose had little effect. Boiling group B streptococcus spent medium failed to affect its vasoactive stimulatory properties. We conclude that in vitro, group B streptococcus synthesizes a heat-stable, non-protein exotoxin that causes human umbilical vein contraction.

Animals↗