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Biomedical subjects

N Hamilton

Publications and source records attributed to N Hamilton.

At least 19 recordsLinked to original sources
PubMed2006

Sensitization to king scallop (Pectin maximus) and queen scallop (Chlamys opercularis) proteins.

OBJECTIVE: To report a case of occupational asthma and urticaria due to the queen scallop (Chlamys opercularis) and king scallop (Pectin maximus). BACKGROUND: A 40-year-old female worked in a shellfish-processing plant, handling king and queen scallops for 5 years. At the time of investigation, she described a 2-year history of work-related respiratory symptoms. METHODS: Serial peak expiratory flow rate readings were recorded and an OASYS study completed. A workplace visit was undertaken and specific immunoglobulin (IgE) radioallergosorbent (RAST) testing of scallop extracts was performed. RESULTS: The OASYS study was consistent with occupational asthma. RAST testing demonstrated evidence of specific sensitization (IgE) to queen and king scallop. There was also some cross-reactivity observed with other shellfish (prawns and crabs). CONCLUSION: Workers exposed to aerosols from scallop species are at risk of occupational asthma and require effective respiratory health surveillance.

Adult↗
PubMed2001

Water-soluble propofol analogues with intravenous anaesthetic activity.

Propofol (2,6-diisopropylphenol) is a widely used intravenous anaesthetic that is formulated as an emulsion since it lacks water solubility. We report a range of water-soluble analogues of propofol, containing a para-alkylamino substituent, which retain good intravenous anaesthetic activity in rodents.

Anesthetics, Intravenous↗
PubMed2000

Randomised controlled trial comparing effectiveness of touch screen system with leaflet for providing women with information on prenatal tests.

OBJECTIVE: To compare the effectiveness of touch screen system with information leaflet for providing women with information on prenatal tests. DESIGN: Randomised controlled trial; participants allocated to intervention group (given access to touch screen and leaflet information) or control group (leaflet information only). SETTING: Antenatal clinic in university teaching hospital. SUBJECTS: 875 women booking antenatal care. INTERVENTIONS: All participants received a leaflet providing information on prenatal tests. Women in the intervention arm also had access to touch screen information system in antenatal clinic. MAIN OUTCOME MEASURES: Women's informed decision making on prenatal testing as measured by their uptake of and understanding of the purpose of specific tests; their satisfaction with information provided; and their levels of anxiety. RESULTS: All women in the trial had a good baseline knowledge of prenatal tests. Women in the intervention group did not show any greater understanding of the purpose of the tests than control women. However, uptake of detailed anomaly scans was significantly higher in intervention group than the control group (94% (351/375) v 87% (310/358), P=0.0014). Levels of anxiety among nulliparous women in intervention group declined significantly over time (P<0.001). CONCLUSIONS: The touch screen seemed to convey no benefit over well prepared leaflets in improving understanding of prenatal tests among the pregnant women. It did, however, seem to reduce levels of anxiety and may be most effective for providing information to selected women who have a relevant adverse history or abnormal results from tests in their current pregnancy.

Attitude to Health↗
PubMed2000

Challenges in the dietary treatment of cystic fibrosis related diabetes mellitus.

Cystic fibrosis related diabetes mellitus is an increasingly recognized problem as survival in patients with cystic fibrosis improves. In a 5 year retrospective study of 627 children and adults attending Toronto cystic fibrosis clinics, we identified 57 (9%) patients with cystic fibrosis related diabetes mellitus; four (1.3%) of 301 children (<18 years) and 53 (16%) of 326 adults. The development of this complication of cystic fibrosis is associated with increased mortality, deteriorations in both respiratory and nutritional status, and the development of late microvascular, but not macrovascular, diabetic complications. Unfortunately, systematic review of the literature provides few well designed studies that provide sound evidence for clinical practice. Recommendations are therefore often based on anecdote, rather than physiological or outcomes research. Dietary therapy combines the principles of the dietary management of both cystic fibrosis and diabetes mellitus, but emphasizes the need for a high energy diet (> 100% of recommended daily intake) in patients with cystic fibrosis related diabetes mellitus. The importance of calories from fat is emphasized, with no restriction on total carbohydrate intake. Insulin intake mirrors carbohydrate intake. Routine dietary therapy is straightforward, but challenges occur due to both complications of cystic fibrosis and advancing disease. If a patient with cystic fibrosis related diabetes mellitus is malnourished, overnight enteral tube feeding is often used, with an adjusted insulin regimen. There is a great need for both physiological and outcomes research to provide sound scientific evidence for the dietary treatment of cystic fibrosis related diabetes mellitus.

Cystic Fibrosis↗
PubMed1998

The genotoxicity and cytotoxicity of dermally-administered cadmium: effects of dermal cadmium administration.

Cadmium, unlike zinc, selenium and copper, has no known biological importance, and therefore, it is classified as a carcinogen in humans, as well as in animals. The effect(s) of levels of dermally-administered cadmium on cadmium genotoxicity and cytotoxicity was investigated in Harlan Sprague-Dawley rats for 14, 21, 28, 35 and 42 days at concentrations of 14 and 28 mg/kg/day. Exposure of rats to cadmium via dermal application caused lesions on the skin (hyperkeratosis, acanthosis and scabbing, alopecia and erythema) and tumors in the scrotum. Anatomical changes, such as distention of the stomach, atrophy of kidney and liver and loss of body weight were also observed in these rats. The toxic effects of cadmium on cell ultrastructure were nuclear membrane damage, chromatin condensation, regression of mitochondrial cristae and ultimately cell death. Analyses of the brain, kidney and liver cells of rats exposed to cadmium, clearly showed DNA damage. Of the three organs examined, DNA from kidney cells sustained the most damage followed by DNA in liver cells. There is a positive correlation between Cd dose(s) and duration of exposure and the extent of DNA damage.

Administration, Cutaneous↗
PubMed1996

The anaesthetic action and modulation of GABAA receptor activity by the novel water-soluble aminosteroid Org 20599.

The anaesthetic profile of a novel water-soluble aminosteroid, Org 20599 [(2 beta, 3 alpha, 5 alpha)-21-chloro-3-hydroxy-2-(4-morpholinyl)pregnan-20-one methanesulphonate], and the ability of the compound to allosterically regulate the activity of the GABAA receptor, have been studied in comparison to the properties of established intravenous general-anaesthetic agents. Intravenously administered Org 20599 produced a rapid onset, short duration loss of the righting reflex in mice. The anaesthetic potency of Org 20599 was comparable to that of the steroids 5 alpha-pregnan-3 alpha-ol-20-one or alphaxalone, and exceeded that of propofol, thiopentone or pentobarbitone. Org 20599 and the reference anaesthetic agents allosterically displaced the binding of [35S]-t-butylbicyclophosphorothionate (TBPS) from GABAA receptors of rat-brain membranes with the order of potency: 5 alpha-pregnan-3 alpha-ol-20-one > Org 20599 > alphaxalone > propofol > thiopentone > pentobarbitone. At human recombinant alpha 1, beta 2, gamma 2L subunit-containing GABAA receptors expressed in Xenopus laevis oocytes, the anaesthetic agents produced a concentration-dependent and reversible potentiation of the peak amplitude of GABA-evoked currents. A similar positive allosteric action of Org 20599 was observed for the GABAA receptors expressed by bovine adrenal chromaffin cells maintained in culture. The rank order of potency in the aforementioned assays was identical to that determined from the displacement of TBPS binding. At concentrations greater than those required for potentiation of GABA, the anaesthetics exhibited GABA-mimetic effects with a rank order of potency that paralleled their modulatory activity. Such direct agonism varied greatly in maximal effect between compounds. The modulatory and direct agonist actions of Org 20599 were additionally confirmed utilizing rat hippocampal neurones in culture. The results indicate Org 20599 to be a potent and short-acting intravenous anaesthetic agent in mice and suggest positive allosteric regulation of GABAA receptor function to be a plausible molecular mechanism of action for the drug.

Anesthetics↗
PubMed1996

Source document position as it affects head position and neck muscle tension.

Measurements of head position, mechanical load at C7, and level of muscle EMG activity in the muscles of the neck were compared across six document positions in both a reading task and a typing (word processing) task. Source documents, identified as a primary visual task, were placed in two positions in front of the subject, flat on the table to each side of the keyboard, and on a document stand at each side of the keyboard. Each of the 20 subjects performed both a reading task and a typing task in each of these document positions while measurements were taken. It was found that the greatest variations in head position occurred in head rotation with documents flat on the table. This document position on each side also produced the greatest level of muscle tension in both the neck extensors and, to a lesser degree, the sternocleidomastoid muscles. In addition, greater variability between document position measures was found in the typing condition.

Adult↗
PubMed1996

Global economic restructuring and international migration: some observations based on the Mexican and Central American experience.

"The purpose of this article is to explore the relationship between processes of global economic restructuring and international migration through an examination of Mexican and Central American immigration to the U.S. and the experiences of Central American and Mexican immigrants in the U.S. This relationship is analysed as one of mutual causation: on the one hand, global restructuring affects conditions in both sending and receiving countries (it is not only a factor in emigration but also in the economic and political receptivity to immigrants at their point of destination); on the other, international migration in turn has an important impact on countries of origin, receiving countries, and the relationship between them." (SUMMARY IN FRE AND SPA)

Americas↗
PubMed1995

High-dose chemotherapy of breast cancer.

High-dose chemotherapy (HDC) with stem cell autografting produces complete remission (CR) rates far in excess of those reported for lower-dose chemotherapy, or for any form of endocrine manipulation in patients with metastatic breast cancer. In early studies involving patients with resistant disease, HDC produced CR rates of as high as 25%. Most contemporary HDC trials accrue patients who are responding to "conventional" chemotherapy, and hence, few untreated patients have been studied in phase II evaluations. In one case, a CR rate of 54% (25% of which remained durable) was reported. In a randomized trial of high-dose versus conventionally dosed therapy, investigators in South Africa reported complete response rates of 50% and 6% respectively. In trials in which HDC is applied as a form of consolidation therapy following "conventional" chemotherapy, complete remission rates as high as 70% are reported.

Antineoplastic Agents↗
PubMed1995

Rapidly cycled courses of high-dose alkylating agents supported by filgrastim and peripheral blood progenitor cells in patients with metastatic breast cancer.

Our purpose was to determine the feasibility of a regimen of multiple, rapidly cycled courses of high-dose alkylating agents, including paired courses of escalating doses of thiotepa, supported by peripheral blood progenitor cells and filgrastim, in patients with responding stage IV breast cancer. The regimen consisted of two courses of cyclophosphamide (3.0 g/m2/course) followed by two courses of thiotepa (500-700 mg/m2/course). All courses were supported by filgrastim. Leukaphereses were performed after each cyclophosphamide course to harvest peripheral blood progenitors (PBPs) for use as rescue following thiotepa administration. The planned interval for all courses was 14 days. Forty-two patients were enrolled. Thirty-eight received all four courses, and four did not receive the second thiotepa cycle due to poor PBP mobilization. The maximum dose of thiotepa that was administered was 700 mg/m2 x 2. At this dose, one patient developed encephalopathy, which resolved over several weeks. The median number of days to an absolute neutrophil count of 0.5 x 10(9)/liter after PBP reinfusion for cycles 1 and 2 of thiotepa were 9 (range, 7-16) and 9 (range, 8-13) days, respectively. The corresponding values for platelet recovery to >20 x 10(9)/liter were 11 (range, 8-39) and 12 (range, 10-28) days, respectively. There were no treatment-related deaths. Hospitalization was required following 28 of 84 cyclophosphamide courses and 76 of 80 thiotepa courses. Four patients developed grade III-IV mucositis. The median interval between courses of treatment was 15 (range, 13-29) days. Of 19 patients who entered the protocol with measurable disease in partial response from prior therapy, 8 (42%) achieved complete response following the high-dose therapy. Nine (21%) of 42 remain progression free at a median follow-up of 28 (range, 20-32) months. Therefore, we concluded that the administration of multiple, rapidly cycled courses of high-dose alkylating agents is feasible.

Adult↗
PubMed1994

High-intensity chemotherapy with peripheral blood progenitor cell support.

In a series of clinical studies at Memorial Sloan-Kettering Cancer Center, we have used hematopoietic growth factors and peripheral blood-derived hematopoietic progenitor cells to facilitate delivery of multiple courses of high-dose chemotherapy at abbreviated treatment intervals. In these studies, we have demonstrated the feasibility of cross-over regimens involving induction chemotherapy with high-dose cyclophosphamide, supported by granulocyte colony-stimulating factor and followed by multiple peripheral blood leukapheresis to harvest progenitor cells. These cells are then used as rescue for the consolidation component of treatment, which, in the earlier-generation studies, consisted of a single course of high-dose carboplatin/etoposide/cyclophosphamide chemotherapy. In subsequent studies, patients received either four courses of high-dose carboplatin or carboplatin/cyclophosphamide or tandem courses of thiotepa. In all cases, the planned interval between treatments was 14 days, and the achieved median was approximately 16 days. These studies show that the administration of high-intensity regimens that deliver multiple courses of very high-dose chemotherapy at relatively brief intervals is feasible. Our current research focuses on exploiting these findings to devise disease-specific regimens for breast and ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

High-intensity chemotherapy with hematopoietic support in breast cancer.

Chemotherapy can produce excellent palliation for many patients with metastatic breast cancer. Survival impact is, however, limited, and permanent remission is extremely rare. There is increasing evidence that dose and dose intensity may be important determinants of outcome in the chemotherapy of breast cancer. Single courses of chemotherapy in doses requiring autologous bone marrow support produce high rates of objective response in patients with metastatic disease that was refractory to prior standard-dose therapy. When used as first chemotherapy for metastases or as consolidation in patients whose disease is responding to lower-dose therapy, high-dose chemotherapy can result in prolonged disease-free survival for some patients. The major cause of treatment failure is relapse from a chemotherapy-induced complete response. Kinetic models suggest that multiple, rapidly cycled courses of high-dose chemotherapy might be superior to single applications or to multiple treatments that are widely spaced in time. Heretofore, the substantial toxicity of high-dose chemotherapy (up to 20% mortality in some early trials) has largely precluded the consideration of timely retreatment; however, the risk appears to have been reduced through the use of hematopoietic growth factors and peripheral blood progenitor cells. Our group has used these new technologies to develop regimens consisting of multiple cycles of high-dose chemotherapy that are rapidly administered. We are currently refining these regimens in preparation for phase II and III studies.

Antineoplastic Agents↗
PubMed1993

Beneficial impact of peripheral blood progenitor cells in patients with metastatic breast cancer treated with high-dose chemotherapy plus granulocyte-macrophage colony-stimulating factor. A randomized trial.

BACKGROUND: This study compared the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or in combination with peripheral blood-derived hematopoietic progenitor cells (PBP) as support for patients receiving high-dose chemotherapy and assessed the adequacy of these strategies as alternatives to autologous bone marrow rescue. METHODS: The authors studied patients with metastatic breast carcinoma who had a major response to conventional chemotherapy or had achieved a complete remission by surgical resection of all known metastases. They were treated with carboplatin 1500 mg/m2, etoposide 1200 mg/m2, and cyclophosphamide 5.0 g/m2. Before this high-dose chemotherapy, the patients had been randomly assigned to one of two hematopoietic support strategies: GM-CSF alone (Group 1) or GM-CSF-primed PBP and GM-CSF (Group 2). Autologous bone marrow was harvested from all patients for use only in the event of persistent pancytopenia with marrow aplasia on day 15. RESULTS: A total of 18 patients were treated. Randomization was halted after the initial 10 patients because of the significant advantages for patients in Group 2 in comparison with those in Group 1 in regard to (1) the median number of days to absolute neutrophil count 0.5 x 10(9)/l (12 versus 21) and platelet count to 50 x 10(9)/l (13 versus 23), (2) platelet transfusions (3 versus 15.5), and (3) episodes of neutropenic sepsis (0 versus 4, respectively). One patient in Group 1 died from treatment-related complications. All patients in Group 1 required bone marrow reinfusion. No patient in Group 2 required bone marrow reinfusion, and no early mortality was observed in this group. Eight subsequent patients were treated with PBP and GM-CSF (Group 3). This group was more heavily pretreated than Groups 1 or 2 and had a slower hematologic recovery than Group 2. However, none of these patients required bone marrow reinfusion. The four patients in Group 1 that did not have early bone marrow rescue all had neutrophil counts of 0.0 on day 15. For Groups 2 and 3, the neutrophil counts on day 15 ranged from 0.3-2.1 x 10(9)/l (median, 1.9) and from 0.2-2.1 x 10(9)/l (median 0.6), respectively. CONCLUSIONS: The use of PBP plus GM-CSF accelerated hematologic recovery after this chemotherapeutic regimen compared with GM-CSF alone; there were reduced morbidity and platelet transfusion requirements. Recovery was sufficiently rapid that PBP were an acceptable alternative to autologous bone marrow transplantation in patients receiving high-dose carboplatin, etoposide, and cyclophosphamide.

Adult↗
PubMed1993

Rapid administration of multiple cycles of high-dose myelosuppressive chemotherapy in patients with metastatic breast cancer.

PURPOSE: To determine the feasibility and safety of a rapidly cycled sequence of high-dose myelosuppressive chemotherapy courses. PATIENTS AND METHODS: Seventeen patients with metastatic breast cancer were treated with two courses of cyclophosphamide (CPA; 3.0 g/m2) supported by granulocyte colony-stimulating factor (G-CSF). Following the first CPA treatment, peripheral-blood leukaphereses commenced when the leukocyte count recovered to 1.0 x 10(9)/L. After hematologic recovery from the second dose of CPA, patients were treated with carboplatin 1,500 mg/m2, etoposide 1,200 mg/m2, and CPA 5.0 g/m2 administered over 3 days. The peripheral-blood progenitors (PBPs) were reinfused 3 days later, and G-CSF was recommenced. RESULTS: All patients received the three courses. The median interval between treatments was 14 days (range, 13 to 21). Sixteen of the 34 courses of CPA resulted in admissions for fever. Following the third course, neutrophil counts recovered to 0.5 x 10(9)/L at a median of 9 days (range, 8 to 18) after PBP reinfusion and platelets recovered to 50 x 10(9)/L at a median of 12 days (range, 9 to 102). There were no treatment-related deaths. Flow-cytometric analysis was performed on the leukapheresis collections of eight patients. Seven patients with at least 2.0 x 10(6) CD34+ CD33- cells per kilogram body weight exhibited prompt hematologic recovery. One patient with 0.03 x 10(6) CD34+ CD33- cells was still cytopenic on day 21, and required reinfusion of her back-up marrow. Among seven patients with measurable or assessable disease, there were two complete responses (CRs) and four partial responses (PRs). CONCLUSION: These preliminary results suggest that multiple, rapidly cycled courses of high-dose myelosuppressive chemotherapy can be administered. PBPs, harvested during the G-CSF-augmented rebound from CPA-induced cytopenia, produce rapid hematologic recovery in patients undergoing high-dose chemotherapy (HDC). Further follow-up will be necessary to assess the efficacy of this specific regimen in the treatment of metastatic breast cancer.

Adult↗