PubMed Health⌕ Search

Biomedical subjects

S Leigh

Publications and source records attributed to S Leigh.

At least 19 recordsLinked to original sources
PubMed1997

Biochemical characterization of recombinant fusions of lipopolysaccharide binding protein and bactericidal/permeability-increasing protein. Implications in biological activity.

The physiological response to endotoxin (lipopolysaccharide (LPS)) can be regulated by two closely related LPS-binding proteins, LPS-binding protein (LBP), which potentiates LPS' inflammatory activity via interaction with the monocytic antigen CD14, and bactericidal/permeability-increasing protein (BPI), which neutralizes LPS. Both proteins bind LPS with high affinity sites in their N-terminal domains, whereas interaction between LBP and CD14 is dependent upon the LBP C-terminal domain. We have created fusions of the N- and C-terminal domains from each protein and compared the functional activities and pharmacokinetics of these fusions, the individual N-terminal domains, and the parent proteins. The N-terminal domains of BPI and LBP bound lipid A with their characteristic apparent affinity constants, regardless of the C-terminal fusion partner. In addition, the C-terminal domain of LBP allowed transfer of LPS to CD14 in conjunction with either N-terminal LPS binding domain. Proteins containing a BPI N-terminal domain had greater heparin binding capacities in vitro and were cleared more rapidly from the plasma of whole animals. Taken together, these data better define how closely related proteins such as BPI and LBP can have opposing effects on the body's response to LPS.

Acute-Phase Proteins↗
PubMed1997

Use of estrogen therapy in a patient with gastrointestinal bleeding secondary to arteriovenous malformations.

OBJECTIVE: To describe a patient with gastrointestinal (GI) bleeding caused by arteriovenous malformations (AVMs) that was treated with estrogen therapy. CASE SUMMARY: A 70-year-old white man was diagnosed with multiple AVMs in the cecum, duodenum, and stomach. Pharmacologic management included the use of ferrous sulfate; however, the patient continued to have recurrent bleeding that required multiple transfusions and endoscopic cauterization. Therapy was initiated with ethinyl estradiol 0.05 mg po qd; no further transfusions have been required for 10 months. DISCUSSION: It is estimated that AVMs of the GI tract account for 1-8% of upper GI bleeding episodes and up to 6% of lower GI bleeding episodes. Hormonal agents have been reported to decrease bleeding in patients with both hereditary and acquired AVMs. CONCLUSIONS: The role of estrogen therapy in treating AVMs of the GI tract is unclear and supported by only one clinical study.

Aged↗
PubMed1997

Comparison of analytical performance and biological variability of three bone resorption assays.

We have compared the analytical performance and biological variability of three commercially available bone resorption assays: Pyrilinks-D, Osteomark, and CrossLaps, for the measurement of urinary free deoxypyridinoline (Dpd), cross-linked N-telopeptides of type I collagen (NTx), and linear C-telopeptides of type I collagen (CTx), respectively. The intraassay and interassay CVs for precision of the Dpd and NTx assays were < 10% for analyte concentrations greater than the second calibrator (i.e., 3 nmol/L Dpd or 30 nmol bone collagen equivalents/L NTx). The CTx assay demonstrated poor precision for analyte concentration lower than the third calibrator (i.e., 200 micrograms/L). The NTx assay exhibited nonlinear recovery for sample dilutions prepared in buffer; however, this nonlinear recovery could be corrected for sample dilutions made in urine at a low analyte concentration. Supplement recoveries of each of the three assays were within 100% +/- 10% on average. All three analytes showed stability through five freeze-thaw cycles. The mean day-to-day variations were 16% for Dpd, and 23% for both NTx and CTx. Similar diurnal rhythm was observed for all three assays on average, with the peak in the early morning and the nadir in the afternoon. Mean amplitude of the diurnal variation was 37% for Dpd and NTx, and 57% for CTx. Variations within the reference intervals for a healthy premenopausal population were 28% for Dpd, 57% for NTx, and 56% for CTx. Pyrilinks-D has demonstrated analytical precision and accuracy equal or superior to Osteomark and CrossLaps in all areas. Dpd exhibits the least biological variability day-to-day, within individuals across the diurnal cycle, and within a healthy premenopausal population.

Adult↗
PubMed1996

An evaluation of the quality of life among long-term survivors of breast cancer.

UNLABELLED: Attention to the quality of life (QOL) among long-term of breast cancer is long overdue. Modest improvements in overall survival have led to a greater emphasis on how women are living with the disease. The purpose of this paper is to report the results of a descriptive study that evaluated the quality of life of 294 breast cancer survivors, and to review the continuum of positive and negative QOL outcomes in this population. Members of the National Coalition for Cancer Survivorship (NCCS) were surveyed and received two QOL instruments: the Quality of Life-Cancer Survivors Tool (QOL-CS) and the Functional Assessment of Cancer Therapy (FACT-G), and a demographic data tool. The main research variables were the subscales (Physical, Psychological, Social, and Spiritual Well-being) and individual items of the QOL-CS and the FACT-G. Results indicated that: a) fatigue, aches and pains, and sleep problems were persistent after treatment ended; b) psychological distress from cancer diagnosis and treatment, and fear of recurrent, metastatic, and recurrent disease were problematic over time; c) family distress, sexuality, and family burden issues were of greatest social concern; and d) uncertainty over the future plagued breast cancer survivors long-term. Breast cancer survivors also reported good outcomes in hopefulness, having a life purpose, and having a positive change after the treatment. CONCLUSIONS: breast cancer survivors experienced long-term changes after completion of treatment which affected overall quality of life. However, many positive benefits were also gained which helped to balance the worse outcomes.

Adult↗
PubMed1996

Survivorship and pancreatic cancer: the role of advocacy.

The past 20 years have witnessed important changes in the manner in which many people with cancer are opting to deal with their disease. In the past, patients yielded to their physicians' treatment choices and assumed that they would be told all they needed to know about their condition. Today, many people with cancer are taking more active, assertive roles, demanding second opinions and treatment option information, and seeking partnerships with their physicians in making decisions and managing their overall health-care programs. This article describes the growing cancer survivorship movement, explores the varying levels of involvement that people with pancreatic cancer may choose, and highlights resources available to help individuals and their families hone their survival skills.

Humans↗
PubMed1995

Quality of life in long-term cancer survivors.

PURPOSE/OBJECTIVES: To describe the quality of life (QOL) of long-term cancer survivors. DESIGN: Descriptive, mailed survey. SETTING: Membership of the National Coalition for Cancer Survivorship (NCCS), which is a nonprofit, peer-support network for people living with cancer. SAMPLE: 687 (57%) of the 1,200 members of NCCS completed the survey. The mean age of the sample was 49.6 years; 81% were female. The predominant cancer diagnoses were breast (43%), lymphoma (9%), ovarian (8%), and Hodgkin's disease (8%). METHODS: Mailed survey using three instruments: a demographic tool, the Quality of Life-Cancer Survivors (QOL-CS) tool, and the Functional Assessment of Cancer Therapy-General (FACT-G) tool. MAIN RESEARCH VARIABLES: Subscale and individual items of QOL including physical, psychological, social, and spiritual well-being. FINDINGS: Results include areas of positive effects for cancer survivors and continued demands of survivorship. Based on scoring of 0 (worst outcome) to 10 (best outcome), cancer survivors' mean QOL-CS subscores were 5.88 for psychological well-being, 6.59 for spiritual well-being, 6.62 for social well-being, and 7.78 for physical well-being. Several demographic factors (e.g., evidence of active disease; female gender; presence of spouse/partner or children; length of time since diagnosis; income) had significant influence on QOL. CONCLUSIONS: Cancer survivors experienced altered lives and had needs related to fear of recurrence and facing the spiritual aspects of having survived a life-threatening illness. IMPLICATIONS FOR NURSING PRACTICE: The growing population of cancer survivors has long-term needs for nursing care that address multidimensional aspects of QOL.

Adaptation, Psychological↗
PubMed1995

Psychosocial morbidity in bone marrow transplant recipients: a prospective study.

Previous work has demonstrated that psychosocial morbidity may occur following bone marrow transplantation (BMT), but few prospective quantitative data are available, especially in adults. We have conducted a prospective psychological assessment of 36 patients accepted onto our BMT programme, of whom 31 proceeded to transplant. Patients were assessed shortly before admission for BMT and again at about 4 and 8 months after the procedure, using the following tools: Hospital Anxiety and Depression Scale (HAD), Social Adjustment Scale-Self Report and the Present State Examination (PSE). A 54% incidence of psychosocial morbidity (as assessed by either an abnormal HAD or PSE result) was found among those cases assessed both before and at least once after BMT. Significant psychosocial morbidity was still present 6-9 months following BMT. Cases scoring abnormally following BMT in general also scored abnormally before transplant, suggesting a predictive value of pre-BMT psychological assessment. Psychological morbidity was unrelated to the type of transplant. Patients with chronic myeloid leukaemia had a higher incidence of post-BMT psychosocial morbidity than patients with other diagnoses; it is suggested that this may be due to their lack of previous experience of intensive haematological therapy. Psychological evaluation may help in identifying patients at risk of post-BMT psychosocial problems.

Adolescent↗
PubMed1993

Expression from the proximal promoter of the carbonic anhydrase 1 gene as a marker for differentiation in colon epithelia.

Carbonic anhydrase 1 (CA1) catalyses the reversible hydration of CO2 and is important for cellular diffusion of CO2, ion transport and pH regulation. The gene encoding CA1 (CA1) has two promoters. In adult colon epithelia the proximal promoter determines high levels of expression and the distal erythroid promoter is repressed. RNA in situ hybridisation shows that CA1 mRNA is abundant in differentiating cells of the colonic crypt as they migrate to the luminal surface, but is not present at the base of the crypts and levels are low on the luminal surface. It is likely that CA1 gene expression in these cells is regulated by differential transcription and/or mRNA stability. In contrast CA1 protein is localised predominantly on the luminal surface. Since CA1 mRNA and protein do not exactly co-localise it can be inferred that CA1 expression is also subject to post-transcriptional control. CA1 mRNA is significantly reduced in colon carcinoma and in adenomas from familial adenomatous polyposis patients. Loss of CA1 expression is associated with the disappearance of differentiated epithelial cells. Out of twelve colon carcinoma cell lines three, LIM1215, LIM1899 and HT115, expressed CA1 and nine did not. This variation in expression may also be associated with cell type differentiation.

Base Sequence↗
PubMed1985

Disposition of mitoxantrone in cancer patients.

We have used a highly sensitive high-performance liquid chromatographic assay to evaluate the pharmacokinetics and tissue disposition of mitoxantrone, an investigational anthracene derivative which has shown significant activity during Phase II clinical trials in the treatment of metastatic breast cancer, unfavorable histology non-Hodgkin's lymphoma, and acute leukemia. Mitoxantrone (12 mg/sq m over 30 to 35 min in 250 ml of dextrose 5% in water) and 14C-labeled mitoxantrone (specific activity, 8.85 muCi/mg) were administered to eight patients who had advanced soft tissue cancers. The plasma disappearance of mitoxantrone concentrations measured by high-performance liquid chromatography was best described by a three-compartment model with a mean t alpha of 0.1 h, a t beta of 1.1 h, and a t gamma of 42.6 h. The mean apparent Vc was 12.2 liters/sq m, while the mean Vd was 1875 liters/sq m. The mean plasma clearance was 0.57 liters/min/sq m, and the mean renal clearance was 45 ml/min/sq m. Only 6.5% of the total mitoxantrone dose was excreted in the urine as unchanged drug over 5 days. The mean recovery of 14C-labeled material in feces over 5 days was 18.3% of the administered dose. Thirty-five days after mitoxantrone administration to a patient who died of progressive kidney cancer, approximately 15% of the 14C dose could be accounted for in seven major organs. We conclude that mitoxantrone appears to distribute into a deep tissue compartment from which it is slowly released. These data provide a pharmacological rationale for use of mitoxantrone on an intermittent dosing schedule.

Anthraquinones↗
PubMed1983

Multiagent chemotherapy in relapsing ovarian cancer.

A multiagent regimen (vinblastine, bleomycin, hexamethylmelamine, and cis-platinum) partly designed on the basis of data from a human tumor stem cell assay was used to treat 36 patients with relapsing epithelial ovarian cancer. All patients included in this study had previously received alkylating agent therapy, and 78% (28/36) had also received Adriamycin. Thirty-five patients were clinically evaluable for response; eight achieved complete clinical remission, and nine achieved partial remission, for an overall response rate of 49%. The median duration of response was 10 months, and three of the complete responders are in remission at 10+, 17+, and 22+ months. Mild to moderate peripheral neuropathy was the major side effect, occurring in 11% (4/35) of patients. Myelotoxicity was well tolerated. We conclude that this four-drug regimen is effective in the treatment of relapsing ovarian cancer patients and should be considered for study as a front-line combination chemotherapy for previously untreated patients.

Altretamine↗
PubMed1977

Nabilone: a potent antiemetic cannabinol with minimal euphoria.

Nabilone is a cannabinol derivative which has potent central antiemetic effects in animals. We observed that the drug significantly reduced the nausea and vomiting induced by cancer chemotherapy in 10 of 13 patients who were refractory to conventional antiemetics. A dose-response effect was apparent. The drug was generally well-tolerated, although it also had sedative effects. Additionally, dizziness, decreased coordination and postural hypotension were observed in some patients. Euphoric effects of the agent were minimal at antiemetic dosage levels.

Adolescent↗