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Biomedical subjects

M Ross

Publications and source records attributed to M Ross.

At least 109 records · Page 6Linked to original sources

Long-range map of a 3.5-Mb region in Xp11.23-22 with a sequence-ready map from a 1.1-Mb gene-rich interval.

Most of the yeast artificial chromosomes (YACs) isolated from the Xp11.23-22 region have shown instability and chimerism and are not a reliable resource for determining physical distances. We therefore constructed a long-range pulsed-field gel electrophoresis map that encompasses approximately 3.5 Mb of genomic DNA between the loci TIMP and DXS146 including a CpG-rich region around the WASP and TFE-3 gene loci. A combined YAC-cosmid contig was constructed along the genomic map and was used for fine-mapping of 15 polymorphic microsatellites and 30 expressed sequence tags (ESTs) or sequence transcribed sites (STSs), revealing the following order: tel-(SYN-TIMP)-(DXS426-ELK1)-ZNF(CA) n-L1-DXS1367-ZNF81-ZNF21-DXS6616- (HB3-OATL1pseudogenes-DXS6950)-DXS6949-DXS694 1-DXS7464E(MG61)-GW1E(EBP)- DXS7927E(MG81)-RBM- DXS722-DXS7467E(MG21)-DXS1011E-WASP-DXS6940++ +-DXS7466E(MG44)-GF1- DXS226-DXS1126-DXS1240-HB1- DXS7469E-(DXS6665-DXS1470)-TFE3-DXS7468E-+ ++SYP-DXS1208-HB2E-DXS573-DXS1331- DXS6666-DXS1039-DXS 1426-DXS1416-DXS7647-DXS8222-DXS6850-DXS255++ +-CIC-5-DXS146-cen. A sequence-ready map was constructed for an 1100-kb gene-rich interval flanked by the markers HB3 and DXS1039, from which six novel ESTs/STSs were isolated, thus increasing the number of markers used in this interval to thirty. This precise ordering is a prerequisite for the construction of a transcription map of this region that contains numerous disease loci, including those for several forms of retinal degeneration and mental retardation. In addition, the map provides the base to delineate the corresponding syntenic region in the mouse, where the mutants scurfy and tattered are localized.

Amino Acid Sequence↗

Translocation between chromosomes 6 and 15 (45,XX,t(6;15)(q25;q11.2)) with further evidence for lack of imprinting of the insulin-like growth factor II/mannose-6-phosphate receptor in humans.

We report a 24 year old female with growth retardation, microcephaly, and congenital abnormalities who has an unbalanced de novo translocation between chromosomes 16 and 6: 45,XX,t(6;15)(q25;q11.2). FISH analysis confirmed that the deletion on chromosome 15 is proximal to the Prader-Willi locus. Several genes have been assigned to the 6q25-qter region including the insulin-like growth factor II/mannose-6-phosphate (IGF-II/M6P) receptor. DNA analysis from our patient documented the loss of one IGF2R gene copy. These data confirm the localisation of the IGF2R receptor to distal 6q25. We also showed reduced expression of the soluble and membrane bound IGF-II receptor, a gene dosage effect incompatible with imprinting. The IGF2R gene has been shown to be imprinted in the mouse but not in humans. Our data provide further evidence for lack of imprinting of this gene in humans.

Adult↗

The motivational impact of temporal focus: thinking about the future and the past.

In this chapter, we consider the degree to which individuals are pulled to behave by their conceptions of the future, pushed to act by their recollections of the past, or primarily driven by current exigencies. In examining conceptions of the future, we discuss how individuals bridge the present and the future, the origin of goals, their impact on behavior and cognition, and the motivational underpinnings for inferring other people's goals. We then outline four theoretical approaches to goal prioritization, the motivational impact of proximal vs distal goals, and the distinction between approaching positive vs avoiding negative outcomes. Turning to conceptions of the past, we discuss the motivational push of the past, the use of the past to select one's goals, the impact current goals have on recall and interpretations of the past, and individual differences in using the past. We conclude that temporal focus provides a meaningful framework for social cognitive approaches to motivation.

Journal Article↗

Effect of foot and ankle MR imaging on clinical decision making.

PURPOSE: To evaluate the effect of magnetic resonance (MR) imaging of the ankle and hindfoot on clinical decision making. MATERIALS AND METHODS: Eighty-one consecutive patients were prospectively examined with MR imaging of the foot and ankle. The referring clinician (one of two orthopedic surgeons or one of two podiatrists) assigned a clinical diagnosis (with a corresponding confidence score of 1-5) and a tentative treatment plan before and after the MR imaging examination and reading. A two-tailed, paired Student t test was used to determine the effects of MR imaging on the diagnosis and treatment. RESULTS: Of the 81 patients examined, 38 (47%) had a post-MR imaging diagnosis that differed from the pre-MR imaging diagnosis (P < .001). Treatment plans were subsequently changed in 28 patients (34%) (P < .001). MR imaging had a statistically significant effect regardless of the assigned, pre-MR imaging clinical confidence rating. MR imaging was also noted to play a key role in surgical planning regardless of the effect on diagnosis. CONCLUSION: MR imaging of the foot and ankle has an effect on clinical decision making. Regardless of the clinician's confidence in diagnosis, MR imaging consistently plays a central role in further defining the diagnosis and treatment.

Adolescent↗

Relationship of the Tufts Quantitative Neuromuscular Exam (TQNE) and the Sickness Impact Profile (SIP) in measuring progression of ALS. SSNJV/CNTF ALS Study Group.

The Tufts Quantitative Neuromuscular Exam (TQNE) is a standardized tool for measuring muscle strength and pulmonary function in patients with amyotrophic lateral sclerosis (ALS). We describe the relationship of TQNE scores to functional disability and health-related quality of life as measured by the Sickness Impact Profile (SIP) in 524 ALS patients. There was a significant relationship (p < 0.0001) between TQNE and SIP scores, both in cross section and over time. TQNE scores strongly relate to ALS patients' quality of life and ability to perform activities of daily living.

Activities of Daily Living↗

A comparison of the psychosocial aspects of AIDS and cancer-related bereavement.

OBJECTIVE: This study compares the psychological symptoms and bereavement distress of individuals bereaved by AIDS with a group bereaved by a cancer death, and addresses the question of whether an AIDS death is associated with a higher rate of adverse psychosocial factors that may increase risk of psychological morbidity in the bereaved individuals. METHOD: AIDS (n = 28) and cancer (n = 30) bereaved individuals (all within 3 months of the bereavement) completed measures of psychological morbidity and measures addressing a range of other adverse factors, e.g., number of losses, levels of social support and stigma. RESULTS: The cancer and AIDS bereaved were essentially similar on all psychological symptom measures. The AIDS group reported lower levels of social support in response to the bereavement than cancer bereaved individuals; a greater number of bereavements, were more likely to conceal the cause of death from significant others including their own family and perceived, in some instances, a greater level of rejection from others. The AIDS group reported higher levels of social support from friends than from family. CONCLUSIONS: At three months following bereavement, AIDS and cancer bereaved were similar in levels of distress. While this may change with the progress of grief over time, it suggests essentially similar early bereavement responses. Those bereaved by AIDS reported a range of other adverse factors such as a greater number of losses, lower social support, stigma, and less open disclosure of the cause of death.

Acquired Immunodeficiency Syndrome↗

High-dose chemotherapy with autologous hematopoietic progenitor cell support for metastatic and high-risk primary breast cancer.

High-dose chemotherapy (HDCT) is being evaluated in the treatment of metastatic and high-risk primary breast cancer. The actuarial 2-year disease-free survival rate for patients with stage IV breast cancer is approximately 15% to 20%. A single metastatic site and achievement of a complete response to induction chemotherapy may be favorable prognostic indicators for disease-free survival after HDCT. Phase II studies in patients with primary breast cancer and > or = 10 and four to nine involved axillary nodes are encouraging. Prospective randomized trials are ongoing in these patient groups. Various strategies are being investigated to reduce the incidence of relapse after HDCT.

Actuarial Analysis↗

HPLC micromethod for amrinone and metabolites in patients receiving concurrent cephalosporin therapy.

Amrinone (AMR), a bipyridine derivative, is receiving increasing use in postoperative cardiac patients as an inotrope and vasodilator. The hemodynamic response to amrinone in adults is linearly related to AMR concentrations, warranting therapeutic drug monitoring. We report a rapid microsample HPLC method for monitoring AMR and its principal metabolites, N-acetyl (N-ac) and N-glycolyl (N-gly) AMR. Serum was precipitated with acetonitrile, and the supernatant fluid was then injected into a C18 narrow-bore column. The mobile phase consisted of a 0.1 mol/L sodium phosphate buffer (pH 6) with a gradient of acetonitrile going from 50 to 100 mL/L of eluent. Detection with a diode-array detector (DAD) concurrently monitored the absorbances at 320 and 345 nm. Monitoring 320 nm allows optimal quantification of AMR, N-gly, and N-ac. Patients often receive concurrent cephalosporin therapy, which is detectable at 320 nm but not 345 nm. Because cephalosporins coelute with AMR or metabolites, monitoring at 345 nm allows separation of these antibiotics from AMR and metabolites while retaining a detection limit of 0.5 mg/L.

Acetonitriles↗

Use of amifostine in bone marrow purging.

One of the main obstacles for the use of high-dose chemotherapy with autologous hematopoietic progenitor cell support in the treatment of malignancies is the possibility of reinfusing clonogenic tumor cells with the hematopoietic graft. Purging of the graft with chemicals can reduce the number of tumor cells but can also damage the normal hematopoietic progenitors. Preclinical studies showed that the phosphorylated sulfhydryl compound amifostine (WR-2721) can protect normal hematopoietic progenitors from damage from alkylating agents. We conducted a randomized clinical trial in patients with breast cancer, non-Hodgkin's lymphoma, and Hodgkin's disease undergoing autologous bone marrow transplant. In this study, patients were randomized to have their bone marrow purged with 4-hydroperoxycyclophosphamide (4-HC) with (arm A) or without (arm B) amifostine. The percentage of colony-forming unit granulocyte-macrophages recovered after purging was higher in the amifostine arm, both in patients with breast cancer and in those with lymphoma, although this difference was not statistically significant. In addition, the time to engraftment was significantly shorter in the amifostine arm in both cohorts. We showed that pretreatment of bone marrow with amifostine prior to purging with 4-HC can protect normal hematopoietic progenitors from damage by 4-HC. This resulted in shorter engraftment rates and less need for supportive care.

Adult↗

Occupational health monitoring practices of registered mercury-using workplaces within Gauteng.

OBJECTIVES: To assess monitoring practices of workplaces registered as mercury users within the then PWV South region of the Department of Manpower (now Gauteng region of the Department of Labour); to identify the main industrial sectors that use mercury and to estimate the number of workers potentially exposed. DESIGN: A descriptive study design was used. SETTING: Workplaces situated in the former PWV South region, as defined by the Department of Manpower. SUBJECTS: Fifty-eight workplaces were registered as mercury users in this region. Postal questionnaires were sent to 34 workplaces on the Department of Manpower's list of mercury users-24 were excluded because they had closed, moved or claimed, on telephonic contact, no longer to use mercury. MAIN OUTCOME MEASURES: Industry type and form of mercury used, monitoring practices and attitudes to legislation. RESULTS: The response rate to the questionnaire was 73.5% (25). Despite being registered as users, 52% (13) of the respondents claimed not to use mercury. Of the 10 mercury-using workplaces, 5 conducted biological monitoring, while only 2 performed environmental measurements. Six of the 10 workplaces used an inorganic form of mercury, 3 used a combination of inorganic and organic mercury, while 1 used organic mercury only. Sixty per cent of all respondents would support legislation that regulated monitoring of mercury in industry. CONCLUSIONS: The study suggests that biological monitoring of mercury is conducted by a limited number of users in Gauteng, while environmental monitoring appears to be neglected. Recently enacted legislation for industrial mercury monitoring needs to be implemented rigorously. Since more than half of the respondents claimed not to use mercury, even though they were registered as users with the Department of Manpower, the study further demonstrates a need to review the system of registration and record-keeping.

Environmental Monitoring↗

Thrombotic microangiopathy as a complication of high-dose chemotherapy for breast cancer.

Five hundred and eighty-one patients with stage II-IV breast cancer were treated at Duke University Medical Center with high-dose chemotherapy, followed by hematopoietic support. All patients received a conditioning regimen of cyclophosphamide, cisplatin and carmustine. Of these patients, 15 (2.6%) developed symptoms similar to the hemolytic-uremic syndrome with evidence of thrombotic microangiopathy (TMA). The time of onset ranged from 75 days to 281 days post-transplant, with a median of 143 days. Hemolytic anemia and thrombocytopenia, without alternative cause, were required for diagnosis. All patients were treated with steroid therapy. In addition, 12 patients were treated primarily with plasmapheresis, and received a median of 46 treatments. Additional therapy included staphylococcal protein A column apheresis (eight patients), vincristine (three patients) and danazol (one patient). The mortality rate was 11 of 15 patients (73%). These patients had a median survival of 41 days from diagnosis of TMA (range 2-76 days). The four survivors are alive at 76, 186, 1837 and 2387 days from diagnosis of TMA. Three of these patients received twice daily plasmapheresis and protein A column apheresis therapy. One patient recovered without specific therapy. TMA is an infrequent complication of high-dose chemotherapy, but is associated with a high mortality. It frequently follows significant pulmonary drug toxicity. Survival may be improved with early diagnosis and aggressive plasmapheresis therapy.

Anemia, Hemolytic↗

High-dose chemotherapy with AHPCS for the treatment of breast cancer. The University of Colorado results.

In summary, the administration of effective high-dose chemotherapy regimens at a time of minimal tumor burden should eradicate disease in selected breast cancer patients who otherwise have little chance of prolonged disease-free survival following standard-dose treatments. The results are particularly promising for breast cancer patients with high-risk stage II/III, and NED or responsive stage IV disease. Many studies to confirm these hypotheses are in progress. New high-dose chemotherapy regimens, together with methods to reduce tumor contamination of the graft and new treatment modalities should improve the current results in patients with breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Paclitaxel-containing high-dose chemotherapy: the University of Colorado experience.

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) is one of the most important antineo-plastic agents developed over the last 20 years. It has proven activity in breast cancer, ovarian cancer, and non-small cell lung cancer. In this study, the possibility of incorporating paclitaxel into a high-dose chemotherapy regimen targeting patients with breast cancer was evaluated. From a widely used regimen composed of cyclophosphamide, cisplatin, and carmustine, carmustine was deleted and paclitaxel added at the beginning of the regimen. The dose of paclitaxel was then escalated until life-threatening toxicities occurred. It was demonstrated that the dose of paclitaxel could be escalated to 775 mg/m2, combined with cyclophosphamide 5,625 mg/m2 and cisplatin 165 mg/m2, followed by autologous hematopoietic progenitor cell support. A phase II study testing this combination in patients with chemotherapy-responsive metastatic breast cancer has been initiated. A new phase I study to test the feasibility of adding carmustine to this paclitaxel-based regimen is currently under way. The status of this study is briefly summarized.

Adult↗

Breaking the silence on elder abuse.

Elder abuse has been described as the silent crime-silent, but not insignificant. The magnitude of the problem for Canadians was revealed in a national survey of 2,000 randomly selected seniors residing in private dwellings: four per cent of respondents reported some form of abuse. The perpetrators were usually people in positions of trust, such as family members or caregivers.

Aged↗