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D C Matthews

Publications and source records attributed to D C Matthews.

42 records · Page 3Linked to original sources

Is there a better way to deliver total body irradiation?

The available data suggest that the antileukemic, immunosuppressive and toxic effects of TBI are highly dose dependent and if TBI is given as single daily fractions at 5-10 cGy/minute, an optimal dose for the treatment of most leukemias is somewhere between 12 and 16 Gy. Giving radiation as a single dose rather than fractionating it increases both its immunosuppressive as well as its toxic effects. The relative anti-leukemic effects of single vs. fractionated irradiation are less clear, but available data support the view that fractionation does not substantially reduce the effects of TBI on myeloid tissue. Increasing the dose rate increases toxicities and, although data are not yet complete, likely increases both immunosuppressive and anti-tumor effects. The impact of total dose, dose fractionation and dose rate are highly interdependent and how best to manipulate these 3 factors to lead to an optimal combination is as yet unknown. Directing radiotherapy to sites of leukemia using monoclonal antibodies or other carriers such as growth factors is feasible and, although there are many aspects of this approach which have yet to be worked out, targeted radiotherapy may prove to be the best way to achieve the therapeutic goals of increased tumor ablation and immunosuppression without increased toxicities.

Bone Marrow Transplantation↗

Radiolabeled anti-CD45 monoclonal antibodies target lymphohematopoietic tissue in the macaque.

Despite bone marrow transplantation, many patients with advanced leukemia subsequently relapse. If an additional increment of radiation could be delivered to lymphohematopoietic tissues with relative specificity, the relapse rate may decrease without a marked increase in toxicity. We have examined the biodistribution of two 131I-labeled monoclonal antibodies reactive with the CD45 antigen in Macaca nemestrina. Three animals received 0.5 mg/kg BC8, an IgG1 of low avidity (6 x 10(7) L/mol). Three received 0.5 mg/kg AC8, an IgG2a of moderate avidity (5 x 10(8) L/mol), and two received 4.5 mg/kg AC8. Estimates of radiation absorbed dose demonstrated that these antibodies could deliver up to five times more radiation to lymph nodes, and up to 2.6 times more to bone marrow, than to lung or liver. The higher avidity AC8 antibody at 0.5 mg/kg was cleared more rapidly from blood and resulted in lower antibody uptake in lymph nodes than did BC8 at 0.5 mg/kg. Increasing the dose of AC8 to 4.5 mg/kg resulted in slower blood clearance and higher lymph node uptake. These studies suggest that radiolabeled anti-CD45 antibodies can deliver radiation with relative specificity to lymphohematopoietic tissues. This approach, in combination with marrow transplantation, may improve treatment of hematologic malignancies.

Animals↗

Prognostic nutritional index in gastrointestinal surgery.

Based on assessment of 161 nonemergency general surgical patients, a multiparameter index of nutritional status was defined relating the risk of postoperative complications to baseline nutritional status. When applied prospectively to 100 gastrointestinal surgical patients, this index provided an accurate, quantitative estimate of operative risk, permitting rational selection of patients to receive preoperative nutritional support.

Digestive System Surgical Procedures↗

Reduction of operative morbidity and mortality by combined preoperative and postoperative nutritional support.

A previously developed and validated predictive nutritional assessment model (Prognostic Nutritional Index) was applied to a heterogenous surgical population. Without knowledge of the then undeveloped PNI, adequate preoperative nutritional repletion (TPN) was provided on clinical indications alone to 50 of 145 patients with the remaining 95 patients receiving no preoperative total parenteral nutrition. Analysis of the two groups found no baseline differences in nutritional status, type and severity of disease and/or operative therapy, and other potentially important variables. In the high-risk stratified group as defined by admission nutritional assessment and calculated PNI (greater than or equal to 50%), adequate preoperative TPN reduced postoperative complications 2.5-fold (p < 0.01), postoperative major sepsis six-fold (p < 0.005) and mortality five-fold (p < 0.01). Clinical "eyeball" evaluation of nutritional status cannot identify high-risk individuals. This nutritional assessment predictive model (PNI) identifies the subset of operative candidates in whom adequate preoperative nutritional support significantly reduces operative morbidity and/or mortality.

Bacterial Infections↗

Clinical practice guidelines in dentistry: Part I. Navigating new waters.

Clinical Practice Guidelines (CPGs) are tools, developed by and for practitioners, to assist in clinical decision making. They are designed to enhance, not replace, clinical judgement and expertise. Well-developed guidelines use the evidence-based approach. The research evidence related to a topic is assembled in a systematic, comprehensive and unbiased manner. Recommendations are made based on the evidence and practitioner feedback is sought prior to formulating the final practice guideline. There are many misperceptions about CPGs and some dentists are wary about their development and use. In this paper, we explore some of the reasons for these misperceptions, review the benefits of sound guidelines, and discuss some of the challenges for guideline development in dentistry in Canada

Canada↗