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Biomedical subjects

D M Ross

Publications and source records attributed to D M Ross.

At least 19 recordsLinked to original sources
PubMed2006

Limited clinical value of regular bone marrow cytogenetic analysis in imatinib-treated chronic phase CML patients monitored by RQ-PCR for BCR-ABL.

Real-time quantitative polymerase chain reaction (PCR) for BCR-ABL mRNA in the peripheral blood (RQ-PCR) provides an accurate and reliable measure of response to therapy in chronic myeloid leukaemia (CML). We wanted to determine in what circumstances additional clinically relevant information was provided by simultaneous cytogenetic analysis in RQ-PCR monitored patients receiving imatinib treatment. We analysed 828 simultaneous RQ-PCR and bone marrow cytogenetic analyses from 183 patients with chronic phase CML with a median follow-up of 20 months. Cytogenetic progression was defined as Philadelphia (Ph)-positive clonal evolution, loss of complete cytogenetic response or an increase of > or = 20% Ph-positive cells. Cytogenetic progression occurred in 24/183 (13%) patients. At the time of cytogenetic progression, none of the 24 patients had a major molecular response (MMR; > or = 3-log reduction in BCR-ABL from standardised baseline). There were 320 RQ-PCR results from 95 patients indicating MMR. No abnormality was detected in any of the corresponding cytogenetic analyses. A policy of regular RQ-PCR monitoring with cytogenetic analysis targetted only to patients who have not achieved, or have lost MMR would represent a rational approach to monitoring and spare most patients the discomfort of multiple marrow aspirates. This approach depends upon availability of an accurate, reproducible RQ-PCR assay with ongoing quality assurance.

Adolescent↗
PubMed2004

Cancer treatment with kinase inhibitors: what have we learnt from imatinib?

Over the past few years, a number of anticancer drugs have been developed that specifically target kinases known to be oncogenic. The leading drug in this area is imatinib mesylate, which targets ABL, KIT and PDGFR. It has been remarkably effective in the treatment of chronic myeloid leukaemia, although resistance remains a significant problem. From the imatinib experience in this setting, we present some principles of kinase inhibition that may have more general applicability in targeted anticancer therapy. It is clear that the identification of appropriate targets (activated kinases) and monitoring levels of response (to recognise emerging resistance) are essential to optimise clinical management.

Benzamides↗
PubMed1997

Folate transport proteins mediate the bidirectional transport of 5-methyltetrahydrofolate in cultured human proximal tubule cells.

Although reabsorption across the apical (AP) membrane of the renal proximal tubule cell plays a vital role in the conservation of plasma 5-methyltetrahydrofolate, basolateral (BL) membrane-directed secretory pathways may also be important in regulating the urinary excretion of folate. Folate transport proteins, folate receptor and the reduced folate carrier have been implicated in the renal conservation of folate across the AP membrane, but their role in BL membrane-directed folate transport has not been studied. 5-Methyltetrahydrofolate transport across the AP and BL membranes of human proximal tubule cells was studied in cells grown on membrane inserts to allow optimum differentiation of AP and BL domains. Colchicine, an inhibitor of vesicular-mediated endocytosis, inhibited AP binding and AP-directed transport without affecting BL transport. Probenecid, an inhibitor of anion exchange, did not affect binding, but inhibited both AP and BL-directed transport with a greater effect on BL transport. Folic acid abolished AP binding of 5-methyltetrahydrofolate, but diminished AP-mediated transport by only 50%. These data suggest that both the folate receptor and the reduced folate carrier participate in AP uptake of folates by human kidney cells, but that BL-mediated uptake occurs primarily by the reduced folate carrier. Folate transport from the secretory direction occurred as readily as that from the reabsorptive direction, indicating that altered secretion could mediate excess urinary folate excretion.

Antidotes↗
PubMed1997

Human visual sensitivity to plumes with a Gaussian luminance distribution: experiments to develop an empirical probability of detection model.

This paper discusses results of a research project designed to develop an empirical model that could be used as a tool to predict human visual sensitivity to plumes. The resultant probability of detection algorithm (PROBDET) allows one to estimate the probability of a plume of known size, shape and contrast being detected visually. As a basis for the algorithm, a series of laboratory experiments using a high threshold signal detection procedure and computer generated images of plumes with Gaussian luminance distributions was conducted to measure human visual sensitivity to plumes. Results of the laboratory experiments are compared with results of contrast sensitivity experiments that examined visual sensitivity to stimuli with square and sine wave luminance distributions. An example of the PROBDET algorithm is presented to demonstrate its potential usefulness for assessing how probability of detection estimates change as plume size and contrast parameters vary. Since this research was designed to build on existing knowledge, a discussion of that knowledge and how it relates to the research conducted is also presented. The focus of this discussion is on the human visual system (HVS) and on how visual sensitivity is affected by factors such as the luminance of the stimulus and the surround, the luminance distribution of the stimulus, the size of the surround, and the size and spatial frequency characteristics of the stimulus.

Adult↗
PubMed1996

Folate transport pathways regulate urinary excretion of 5-methyltetrahydrofolate in isolated perfused rat kidney.

The reabsorption of 5-methyltetrahydrofolic acid (5-CH3-H4PteGlu) by the renal proximal tubule has an important role in the maintenance of plasma folate concentrations. However, the mechanism by which this vitamin traverses the renal epithelium remains to be determined. Studies in cultured cells have suggested that the folate receptor in association with a probenecid-sensitive anion carrier may be involved in the transmembrane transport of the vitamin. Because 5-CH3-H4PteGlu is reabsorbed and metabolized in the isolated perfused rat kidney (IPRK) in a smaller manner to in vivo models, the IPRK was used to evaluate pathways involved in folate reabsorption. Reabsorption of 5-CH3-H4PteGlu could not be saturated in the isolated perfused rat kidney, even at concentrations up to 2 mumol/L. Folic acid (PteGlu) was used as a competitive inhibitor of FR-dependent reabsorption of 5-CH3-H4PteGlu. When 5-CH3-H4PteGlu was maintained at 1 nmol/L (a concentration at which receptor-mediated transport should be maximal), PteGlu (up to 100 nmol/L) had no effect on reabsorption. The addition of probenecid (1 mmol/L) did not affect the reabsorption of 5-CH3-H4PteGlu but inhibited the fractional excretion of the anion para-aminohippurate. Probenecid also inhibited the urinary excretion of 5-CH3-H4PteGlu metabolites, indicating that reabsorbed 5-CH3-H4PteGlu was metabolized to products that were subsequently secreted into the urine by anion exchange pathways. The physiological importance of a folate receptor-mediated reabsorption of 5-CH3-H4PteGlu appears to be minor in the isolated perfused rat kidney, whereas nonspecific pathways appear to play a major role in the renal folate reabsorption.

Analysis of Variance↗
PubMed1992

Emotional support for patients with cancer who are undergoing CT: semistructured interviews of patients at a cancer institute.

To understand and improve the experience of cancer patients undergoing computed tomography (CT), 79 patients who underwent CT at a cancer institute participated in semistructured interviews about their experiences with CT. All patients had previously undergone CT; 75% (n = 59), three times or more. Anxiety about results was the most common concern during first and subsequent CT examinations. Technical aspects were a common concern during initial scanning, but not subsequently. Methods of relaxation most used by patients during CT were following instructions (56% [n = 44]), meditating and visualizing (44% [n = 35]), and praying (42% [n = 33]). Patients suggested several ways in which the radiology staff can support them during the evaluation of their malignancy. Fifty-five (70%) of the patients said they would like the radiologist to tell them the results of their scanning. Optimal care of patients with cancer who undergo CT goes beyond technical to emotional and spiritual support.

Anxiety↗
PubMed1992

Difference between nurses' and physicians' approach to denial in oncology.

A psychiatrist and a psychiatric nurse interviewed 33 physicians and 94 nurses at a cancer center about their experience working with oncology patients, including their usual approach to "denial" seen in these patients. Most respondents viewed denial as a useful, nearly universal defense mechanism, potentially capable of interfering with treatment. Physicians described a pattern in which their patients were presented with the facts one time during diagnosis and formulation of a treatment plan, after which denial was allowed and new facts not offered unless the denial was viewed as interfering with the medical intervention. Nurses more often referred to denial as a phase, stressing the importance of honesty in dealing with patients who are prone to deny. They experienced discomfort when patients who were suffering adverse effects of treatment seemed to need greater honesty from their physicians. Discussion of these differences includes the effect of the contexts in which nurses and physicians encounter denial as well as their complementary roles in patient care, and the differential goals and values of the two professions.

Adult↗
PubMed1992

Relationships with patients in oncology: can a clinician be a friend?

Encounters with patients who are experiencing a life crisis such as cancer can be profoundly meaningful to both patients and those caring for them. Intense emotional involvement with patients can also lead to difficulties including "burnout" (Davitz and Davitz 1975), interstaff conflict (Burnham 1966; Pollack and Battle 1963; Robinson 1984; Weintraub 1964), and violation of professional boundaries (Applebaum 1990; Gartrell et al. 1986; Gutheil 1989a, 1989b). Nicholi (1988) has reviewed the challenges that psychotherapists face in maintaining relationships with patients that are both close and therapeutic. However, there has been little research into the relationships that clinicians in other medical disciplines have with their patients. This report describes both the stresses and rewards of relationships with oncology patients in a comprehensive sample of 192 staff members at a regional cancer center, interviewed about factors affecting their job satisfaction.

Adult↗
PubMed1991

Presenting a diagnosis of cancer: patients' views.

BACKGROUND: Although in general, patients in the United States are now told if they have been diagnosed as having cancer, little information is available either about the way in which this is done or about patients' satisfaction with how they are told. METHODS: Thirty-two patients were interviewed who had been given a diagnosis of cancer; one half were being treated at a comprehensive cancer center and one half at a community hospital. The study instrument, presented in a semistructured interview conducted by psychosocial clinicians, included specific questions about the setting and the manner in which the patients were told, their reactions to the diagnosis, and their suggestions of how physicians should inform others who have to be informed of a similar diagnosis. RESULTS: All patients were told of their diagnosis by a physician; 84% of the time the diagnosis was given in person. Patients said that being told with hope, information, and caring, and with respect for their privacy and wishes to have a supportive person present were particularly helpful. Almost 40% of patients reported at the time of the interview that their hopes were directed toward remission and optimal quality of life rather than toward a cure. Four of the six patients whose conditions had initially been misdiagnosed described subsequent mistrust of information received from physicians. CONCLUSIONS: These findings confirm the importance of a physician providing hope for and fostering trust in patients to whom they are presenting the diagnosis of cancer. The results indicate that physicians' help in providing treatment information contributes more to hope than does cheerfulness or optimism, and that patients who have been given a misdiagnosis require special consideration in order to reestablish trust.

Adult↗
PubMed1984

Homograft aortic root replacement for complicated prosthetic valve endocarditis.

Ten patients with late-onset prosthetic valve endocarditis, uncontrolled sepsis, and aortic root abscesses underwent homograft aortic root replacement with reimplantation of the coronary arteries. There were two perioperative deaths. The necrotizing endocarditis was cured in all eight survivors, who have been followed from 6 to 132 months (mean 3 1/2 years). Two of these patients are having symptoms caused by biological valve malfunction; excellent clinical and hemodynamic results have been obtained in the remaining six patients. Homograft aortic root replacement excludes the root abscesses and the weakened infected aortic anulus from the high systemic pressures and permits suturing to a bed of the aortic root in continuity with healthy myocardium. This operation provides an alternative technique to the management of selected patients with active prosthetic infection and destruction of the aortic ring by sepsis.

Abscess↗