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Biomedical subjects

P Ross

Publications and source records attributed to P Ross.

At least 19 recordsLinked to original sources
PubMed2001

Effects of acid treatment on the trace metal content of chromatographic silica: bulk analysis, surface analysis and chromatographic performance of bonded phases.

A series of studies has been carried out on the effect of refluxing silica chromatography particles for 0.5 h and 18 h in water, dilute hydrochloric acid and dilute hydrofluoric acid. The bulk and surface trace metal concentrations were measured by inductively-coupled plasma atomic emission spectroscopy, static secondary ion mass spectrometry (SSIMS) and X-ray photoelectron spectroscopy. Diffuse reflectance Fourier transform infrared spectroscopy was used to determine changes in 'isolated" and "bonded" silanol groups. The chromatographic behaviour of a series of weakly basic analytes was investigated on C8 and C18 bonded phases manufactured from the acid-treated silicas. The different reflux treatments all resulted in a reduction in the numbers of isolated silanols compared with the untreated silica and SSIMS analysis suggested that the HF-treated silicas had undergone a more efficient surface rehydroxylation. Bulk trace metals were removed most effectively by the HF treatment, with the multivalent elements (Ti and Al) being the most difficult to remove. Surface specific analysis suggested that trace metals were removed more rapidly from the surface of the silica compared to the bulk matrix and that the acid treatments resulted in halide contamination of the silica surface. Evidence is presented to suggest that the bulk metal content of the silica is not representative of the concentration of metals at the chromatographic surface. The chromatographic investigations showed that the HF-treated silica gave substantially better performance towards weak bases than the HCl-treated silicas.

Acids↗
PubMed2000

Chromatographic aspects in high throughput liquid chromatography/mass spectrometry.

Important parameters to consider when developing a liquid chromatography/mass spectrometry (LC/MS) method are buffer type and concentration, and column geometry. In the work presented here the choice of buffer for the analysis of basic compounds using a polar embedded phase (HyPURITYtrade mark ADVANCE) is illustrated for the analysis of tricyclic antidepressants. Method transfer from a 4.6 mm i.d. column to a 2.1 mm i.d. column is demonstrated for the analysis of triazines and anabolic steroids and their metabolites, with no change in selectivity and with added speed of analysis. Analysis of eight beta-blockers is achieved in 65 seconds by using a short 30 x 4.6 mm C18 column.

Adrenergic beta-Antagonists↗
PubMed2000

A clinical nomogram for predicting long-term survival in advanced colorectal cancer.

From our prospectively accrued database of patients with gastrointestinal cancer, 1057 patients with advanced colorectal cancer were identified with the aim of determining predictive factors for survival of greater than 2 years and to use this information to develop a predictive nomogram. Patient's baseline characteristics, type and number of chemotherapy regimens received, and response to chemotherapy were assessed by univariate and multivariate logistic regression comparing those who survived greater than or less than 2 years. A total of 161 (15.2%) patients survived more than 2 years, so-called long survivors (LS). In multivariate analysis, positive predictive factors for LS were: good performance status (PS), normal serum carcinoembryonic antigen (CEA), rectal primary, Dukes' stage A-B, well or moderate differentiation, two or less disease sites, response to chemotherapy and treatment used protracted venous infusion (PVI) 5-fluorouracil (5-FU) in first-line chemotherapy, and the increasing number of chemotherapy treatments received. From these PS, CEA, number of sites and response to first-line chemotherapy were used to develop a nomogram capable of predicting the probability of survival beyond 2 years for an individual patient. This large study confirmed the relevance of known prognostic factors in metastatic colorectal cancer and demonstrated the importance of response to chemotherapy as an independent factor to predict LS. By combining these, we developed a nomogram which provides information which is likely to prove useful in the management of patients with advanced colorectal cancer.

Adolescent↗
PubMed2000

Effects of growth hormone treatment on red cell plasma membrane fatty acid constituents in hypopituitary adults.

The effects of replacement with recombinant human GH (hGH) on red cell plasma membrane fatty acid and cholesterol constituents were assessed in nine adult patients with growth hormone deficiency. They were treated with hGH in a dose of 0.125 U.kg-1.wk-1 for four weeks and at 0.25 U.kg-1.wk-1 thereafter for an overall mean duration 13.5 +/- 3.9 months (mean +/- SD). The relative proportions of the various phospholipid fatty acid constituents and the proportion of cholesterol in the phospholipid bilayer were assayed every six months. At the end of the study, the percentage of arachadonic acid (20:4) in membrane phospholipid was found to rise by an average of 3.7% (P < 0.05) and there appeared to be a nonsignificant trend showing an increase in highly unsaturated fatty acids, namely linoleate (18:2) and gamma linolenic acid (18:3) and a corresponding decrease in unsaturated fatty acids, namely palmitate (16:0) and stearate (18:0) and monounsaturated fatty acids such as palmitoleic acid (16:1), oleic acid (18:1) and oleic acid isomer (18:1 iso). In addition, the proportion of cholesterol in the plasma membrane i.e. the cholesterol/phospholipid ratio was found to decrease by 0.84% (P < 0.05). There was a significant increase in HbAlc from 4.85 +/- 0.51 to 4.94 +/- 0.45% (P < 0.01) by the end of the study.

Adult↗
PubMed2000

Quantitative approach to single-nucleotide polymorphism analysis using MALDI-TOF mass spectrometry.

Pooling of DNA samples before genotyping is a valuable means of streamlining large-scale genotyping efforts in disease association studies, single-nucleotide polymorphism (SNP) validation or mutant allele screening programs. In this report, we explore the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to quantitative analysis of SNPs. The measurements are based on MALDI-TOF MS analysis of primer extension assays performed on standard mixtures of pooled PCR products at several test loci. The inherent high molecular weight resolution of MALDI-TOF MS conveys high specificity and good signal-to-noise ratio for performing accurate quantitation. The methods described maximize the sensitivity and quantitative capacity of MALDI-TOF MS while preserving the throughput and economic advantages of the MALDI-TOF platform. Using the format described, we demonstrate that allele frequencies as low as 5% can be detected quantitatively and unambiguously.

Alleles↗
PubMed2000

Smooth muscle tumor of the pleura. A case report and review of the literature.

Smooth muscle tumors of the serosal membranes are extremely rare and have received little attention in the literature. To the best of our knowledge, only 1 published series of 5 pleural smooth muscle neoplasms has been published to date. We describe a primary pleural neoplasm with smooth muscle differentiation documented by light microscopy, immunohistochemistry, and electron microscopy. This tumor originated in the parietal pleura in a 32-year-old white man and was diagnosed incidentally by chest radiography; the diagnosis was confirmed by magnetic resonance imaging and biopsy. Four years later, the tumor was noted to have increased in size and disseminated into the chest wall as a separate circumscribed mass located in the pectoral muscle. Both masses were resected and diagnosed as smooth muscle tumors. We conclude that smooth muscle tumor of the pleura is a well-defined entity with a low, but definite malignant potential; therefore, we recommend complete resection and long-term follow-up for all patients.

Actins↗
PubMed2000

Implementing the Agency for Health Care Policy and Research's Smoking Cessation Guideline in a lung cancer surgery clinic.

PURPOSE/OBJECTIVES: To determine the effectiveness of a nurse-managed smoking cessation intervention based on the Agency for Health Care Policy and Research's (AHCPR's) Smoking Cessation Guideline in a lung cancer surgery clinic. DESIGN: Quasi-experimental. SETTING: Urban, Midwest, academic, and tertiary care. SAMPLE: 25 adult male and female smokers with a confirmed diagnosis of lung cancer that had been surgically managed. Subjects were assigned to an intervention group (n = 14) or a usual-care group (n = 11). METHODS: Participants in the intervention group received a nurse-delivered, AHCPR-based smoking cessation intervention that included face-to-face and phone follow-up contact beginning with the first preoperative clinic consultation. Usual-care participants received routine care provided at the institution. MAIN RESEARCH VARIABLES: Self-reported smoking status with expired air carbon monoxide confirmation six months postsurgery. FINDINGS: Seventy-one percent of the intervention group was biochemically confirmed to be abstinent by expired air carbon monoxide, as compared to 55% in the usual-care group. CONCLUSIONS: Smokers diagnosed with lung cancer desired to quit smoking and may benefit from an intensive smoking cessation intervention at time of diagnosis. IMPLICATIONS FOR NURSING PRACTICE: Further research should include continuing evaluation of an intensive smoking cessation intervention with this population, and all clinicians should be trained to implement AHCPR's Smoking Cessation Guideline in practice.

Adult↗
PubMed2000

Oncological applications of gene therapy.

Despite the rapid technological advances that continue to sustain the field of cancer gene therapy, few individual patients have benefited from the revolution so far. The plethora of clinical trials described confirms that each malignancy will have its own ideal strategy based on the associated molecular defects, and there has been rapid progress from this viewpoint. At the same time, there has been a renewed appreciation for the limitations to gene therapy, which include low efficiency of gene transfer, poor specificity of response and methods to accurately evaluate responses, and lack of truly tumor-specific targets at which to aim. As with all new therapies, we are climbing a steep learning curve in terms encountering treatment-related toxicities, as well as profound ethical and regulatory issues.

Animals↗
PubMed2000

Gene therapy: recent progress in the clinical oncology arena.

Despite the rapid technological advances that continue to sustain the field of cancer gene therapy, few individual patients have benefited from the revolution so far. The plethora of clinical trials described confirms that each malignancy will have its own ideal strategy based on the associated molecular defects, and there has been rapid progress from this viewpoint. At the same time, there has been a renewed appreciation for the limitations to gene therapy, which include low efficiency of gene transfer, poor specificity of response and methods to accurately evaluate responses, and lack of truly tumor-specific targets at which to aim. As with all new therapies, we are climbing a steep learning curve in terms encountering treatment-related toxicities, as well as profound ethical and regulatory issues.

Animals↗
PubMed1999

Cloning and localization of Rab3 isoforms in bovine, rat, and human parathyroid glands.

Rab3 proteins are small GTP-binding proteins known to play a role in regulated exocytosis processes. This study examines the expression of Rab3 mRNA and protein in bovine, rat and human parathyroid glands. mRNAs of several Rab3 isoforms were detected in bovine (Rab3A, Rab3B and Rab3C) and rat (Rab3A, Rab3B and Rab3D) parathyroid glands by RT-PCR and sequencing. Rab3A protein was detected in the cytosolic extract from bovine parathyroid gland by Western blotting using a monoclonal antibody for Rab3A. Rab3A protein was localized to parathyroid hormone-containing chief cells by immunohistochemical staining. Subcellular localization of Rab3A protein by immunogold electron microscopy revealed that the majority of Rab3A protein was not associated with dense-core vesicles, but localized in the cytosol of the chief cells. Altogether, our results demonstrate that Rab3 isoforms are expressed in parathyroid chief cells, suggesting that they may play a role in regulated exocytosis in these cells.

Animals↗
PubMed1999

Improving electrotransfection efficiency by post-pulse centrifugation.

We have demonstrated that the viability of electrotransfected adherent CHO and suspended NK-L, K-562, L1210 and MC2 cells is improved if pelleting by centrifugation is performed immediately after pulsing. The protection effect on cell viability is cell line- and pellet thickness-dependent. For forming CHO cell pellets, centrifugation force (300-13,000 g) and duration are not crucial; about five to 10 cell layers in the pellet provide the optimal protection effect. NK-L, K-562, L1210 and MC2 cell pellets are optimally formed by centrifugation at 13,000 g in an Eppendorf desktop centrifuge. Pelleting improves the cell viability over the whole range of the NK-L, K-562, L1210 and MC2 cell concentrations studied. When this pelleting method is applied to load CHO cells with FITC-dextran (41,000 MW), not only is the success rate close to 100%, but the growth rate is similar to the control, which is far better than the conventional electroporation method. Furthermore, the transfection efficiency of the five cell lines in pellet is significantly higher than that in suspension.

Animals↗
PubMed1999

The study of the process of fluid-phase endocytosis in cervical squamous cells using fluorescent microspheres.

Physiological processes in cervical squamous epithelium have not been extensively studied. Perhaps understandably, most of the research has concentrated on the pathology of the cervix, in particular dysplasia and malignancy. Fluid-phase endocytosis is a physiological process which has been demonstrated to be important in understanding disease development at other squamous epithelial sites, e.g. oesophagus. In this study, we have demonstrated by a new methodology developed in our laboratory using fluorescent microspheres and flow cytometry that fluid-phase endocytosis occurs in cervical squamous cells. The process has been shown to be dose- and time-dependent. This novel approach provides a means to improve our understanding of the physiological functions of the cervix and may provide insight into the pathogenesis of cervical neoplastic and non-neoplastic disease.

Cervix Uteri↗
PubMed1998

Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group.

BACKGROUND: Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the balance between its long-term risks and benefits remains unclear. Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear. METHODS: We studied the effect of 2.5 mg or 5 mg of alendronate per day or placebo on bone mineral density in 1174 postmenopausal women under 60 years of age. An additional 435 women who were prepared to receive a combination of estrogen and progestin were randomly assigned to one of the above treatments or open-label estrogen-progestin. The main outcome measure was the change in bone mineral density of the lumbar spine, hip, distal forearm, and total body measured annually for two years by dual-energy x-ray absorptiometry. RESULTS: The women who received placebo lost bone mineral density at all measured sites, whereas the women treated with 5 mg of alendronate daily had a mean (+/-SE) increase in bone mineral density of 3.5+/-0.2 percent at the lumbar spine, 1.9+/-0.1 percent at the hip, and 0.7+/-0.1 percent for the total body (all P<0.001). Women treated with 2.5 mg of alendronate daily had smaller increases in bone mineral density. Alendronate did not increase bone mineral density of the forearm, but it slowed the loss. The responses to estrogen-progestin were 1 to 2 percentage points greater than those to the 5-mg dose of alendronate. Alendronate was well tolerated, with a safety profile similar to that of placebo or estrogen-progestin. CONCLUSIONS: Alendronate prevents bone loss in postmenopausal women under 60 years of age to nearly the same extent as estrogen-progestin.

Alendronate↗
PubMed1998

Clinical report on long-term bone density after short-term EMF application.

A 1984 study determined the effect of a 72 Hz pulsating electromagnetic field (PEMF) on bone density of the radii of post-menopausal (osteoporosis-prone) women, during and after treatment of 10 h daily for 12 weeks. Bone mineral densities of the treated radii increased significantly in the immediate area of the field during the exposure period and decreased during the following 36 weeks. Bone density determination of the radii of these women, remeasured after eight years, suggests no long-term changes. The bone density-enhancing effect of PEMFs should be further studied, alone and in combination with exercise and pharmacologic agents such as the bisphosphonates and hormones, as prophylaxis in the osteoporosis-prone postmenopausal woman and as a possible block to the demineralization effect of microgravity.

Absorptiometry, Photon↗
PubMed1998

Correlation of CT with histopathological findings in patients with gastric and gastro-oesophageal carcinomas following neoadjuvant chemotherapy.

UNLABELLED: Gastric carcinoma is the fourth commonest cause of death from malignant disease in United Kingdom. In the Western hemisphere, it usually presents with advanced disease, which contributes to its very poor prognosis. Pre-operative (neoadjuvant) chemotherapy offers the possibility of down-staging such tumours and the potential to render tumours operable. Computed tomography (CT) plays a central role in the assessment of patients presenting with the disease, and in those who undergo chemotherapy, in evaluating their response. OBJECTIVE: This study was undertaken to evaluate the role of CT in predicting loco-regional spread of tumour following neoadjuvant chemotherapy in non-metastatic gastric and gastro-oesophageal cancers. METHODS AND MATERIALS: We correlated CT evidence of loco-regional spread with pathological findings following surgery in 21 patients who received pre-operative chemotherapy. RESULTS: Residual masses were seen on CT in 19 patients, and 15 contained active tumour, although in four patients no viable tumour was demonstrated at histopathology. The overall accuracy of CT in assessing loco-regional disease was disappointing with sensitivities, specificities, positive and negative predictive values of 57%, 43%, 75% and 33%, respectively. CONCLUSIONS: We conclude that CT is not accurate in identifying residual loco-regional spread and therefore should not preclude surgery in those patients who have received neoadjuvant chemotherapy.

Adult↗
PubMed1998

High level multiplex genotyping by MALDI-TOF mass spectrometry.

A primer extension assay is used to perform highly multiplexed genotyping of single nucleotide polymorphisms (SNPs) present in genomic DNA amplified by a multiplex PCR. The assay uses matrix-assisted laser desorption ionization time-of-flight mass spectrometry to accurately measure the masses of short oligonucleotide primers extended by a single dideoxynucleotide. The multiplexed genotyping assays rely on the natural molecular weight differences of DNA bases. By careful analysis of primer composition complementary to the target, or by judicious addition of one or more noncomplementary 5' bases to the genotyping primers, mass spectra of interleaved genotyping products can be generated with no ambiguity in allele assignment. Using a model multiplex PCR system, we demonstrate the ability to perform 12-fold multiplex SNP analysis.

Base Sequence↗
PubMed1998

The Royal Marsden experience of a small bowel adenocarcinoma treated with protracted venous infusion 5-fluorouracil.

The purpose of this study was to review the efficacy of a protracted venous infusion of 5-fluorouracil (PVI 5-FU)-based chemotherapy in advanced small bowel adenocarcinoma. Data on all patients with small bowel malignancy who were seen at a single institution over a 5-year period were retrieved from the gastrointestinal unit and hospital databases, and these cases were reviewed. Eight patients with advanced small bowel adenocarcinoma received PVI 5FU-based chemotherapy. The overall response rate in assessable patients was 37.5% (3/8). The median overall survival was 13 months (range 1-28), and progression-free survival was 7.8 months (range 0-15). Overall, the treatment was well tolerated and symptomatic benefit was seen. In conclusion, PVI 5-FU has activity in this disease. This should be assessed either as a single agent or as part of a combination regimen such as epirubicin/cisplatin/PVI FU (ECF) in a multicentre randomized study.

Adenocarcinoma↗